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  • 1
    Electronic Resource
    Electronic Resource
    Short-term treatment with GLP-1 increases pulsatile insulin secretion in Type II diabetes with no effect on orderliness (2000)
    Springer
    Diabetologia 43 (2000), S. 583-588 
    Details
    ISSN: 1432-0428
    Keywords: Keywords GLP-1 ; Insulin ; pulsatility ; insulin secretion ; time series ; Type II diabetes ; human.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. The enteric incretin hormone, glucagon-like peptide-1 (GLP-1), is a potent insulin secretagogue in healthy humans and patients with Type II (non-insulin-dependent) diabetes mellitus. In this study we assessed the impact of short-term GLP-1 infusion on pulsatile insulin secretion in Type II diabetic patients. Methods. Type II diabetic patients (n = 8) were studied in a randomised cross-over design. Plasma insulin concentration time series were obtained during basal conditions and during infusion with saline or GLP-1 (1.2 pmol/l · kg–1· min–1) on 2 separate days. Plasma glucose was clamped at the initial concentration by a variable glucose infusion. Serum insulin concentration time series were evaluated by deconvolution analysis, autocorrelation analysis, spectral analysis and approximate entropy. Results. Serum insulin concentrations increased by approximately 100 % during GLP-1 infusion. Pulsatile insulin secretion was increased as measured by secretory burst mass (19.3 ± 3.8 vs 53.0 ± 10.7 pmol/l/pulse, p = 0.02) and secretory burst amplitude (7.7 ± 1.5 vs 21.1 ± 4.3 pmol/l/min, p = 0.02). A similar increase in basal insulin secretion was observed (3.6 ± 0.9 vs 10.2 ± 2.2 pmol/l/min, p = 0.004) with no changes in the fraction of insulin delivered in pulses (0.50 ± 0.06 vs 0.49 ± 0.02, p = 0.84). Regularity of secretion was unchanged as measured by spectral analysis (normalised spectral power: 5.9 ± 0.6 vs 6.3 ± 0.8, p = 0.86), autocorrelation analysis (autocorrelation coefficient: 0.19 ± 0.04 vs 0.18 ± 0.05, p = 0.66) and the approximate entropy statistic (1.48 ± 0.02 vs 1.51 ± 0.02, p = 0.86). Conclusion/interpretation. Short-term stimulation with GLP-1 jointly increases pulsatile and basal insulin secretion, maintaining but not improving system regularity in Type II diabetic patients. [Diabetologia (2000) 43: 583–588]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051347
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacodynamics and pharmacokinetics of intravenous glibenclamide in Caucasian and Chinese patients with type-2 diabetes (2000)
    Springer
    European journal of clinical pharmacology 55 (2000), S. 721-727 
    Details
    ISSN: 1432-1041
    Keywords: Key words Glibenclamide ; Insulin ; Proinsulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: We analysed the kinetics and effects of glibenclamide (Gb) on glucose, insulin and proinsulin secretion in two ethnic groups (10 in each) of type-2 diabetic patients, one of Caucasian, the other of Chinese origin. Background: Diabetes mellitus type 2 is a global disease affecting all ethnic groups. There are ethnic differences in both the prevalence and metabolic characteristics of the disease. Important interethnic pharmacodynamic and pharmacokinetic differences have been reported for several drugs. With few exceptions, detailed studies on sulphonylurea are lacking. Material and methods: The patients were studied on two occasions when either no Gb (control) or 1.25 mg Gb was administered i.v., immediately before the administration of a 75-g oral glucose tolerance test. Concentrations of insulin and proinsulin were determined by means of radioimmunoassay without cross-reactivities. Gb concentration was determined using high-performance liquid chromatography. Pharmacodynamic results were calculated using net areas under the curves, with basal values set as zero. A P value less than 0.05 was considered significant. Results: When glucose was administered orally without Gb, Chinese patients had higher plasma glucose increases at 10 min (7.6 mmol/l × min vs 2.6 mmol/l × min) and higher increases of plasma insulin levels than Caucasians at both 10 min (198 pmol/l × min vs 54 pmol/l × min) and 30 min (2286 pmol/l × min vs 1198 pmol/l × min). When Gb was administered, the plasma glucose increases were reduced, and the increases of serum insulin and proinsulin levels were greater in both ethnic groups. Compared with the basal values (−1 min), proinsulin/insulin ratios (RPI) were lowest at 10–30 min, followed by an increase. Chinese patients had higher increases of serum insulin levels at 10 min (1109 pmol/l × min vs 550 pmol/l × min) and a lower RPI at 30 min (6.0% vs 7.6%) and 240 min (15.0% vs 21.0%) relative to Caucasians. Serum Gb data were best fitted to a biexponential i.v. model. There were no interethnic differences in any of the pharmacokinetic parameters. Conclusion: In summary, following oral glucose administration without Gb, Chinese type-2 diabetic patients had higher plasma insulin levels but also higher plasma glucose levels during the first 10 min, which might reflect reduced insulin sensitivity or more rapid glucose absorption. Gb augmented glucose-induced release of both insulin and proinsulin in both ethnic groups; the effect on insulin secretion was more pronounced. In conclusion, minor pharmacodynamic but no pharmacokinetic differences were found between the two groups. It seems appropriate to employ the same dosage principles when using Gb in Caucasians and Chinese.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050004
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  • 3
    Electronic Resource
    Electronic Resource
    Growth, puberty and hypothalamic-pituitary function in children with suprasellar arachnoid cyst (2000)
    Springer
    European journal of pediatrics 159 (2000), S. 348-355 
    Details
    ISSN: 1432-1076
    Keywords: Key words Arachnoid cyst ; Growth ; Growth hormone deficiency ; Growth hormone treatment ; Insulin ; Leptin ; Puberty ; Precocious puberty
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A suprasellar arachnoid cyst may cause disorders of growth, puberty and hypothalamic-pituitary function, due to the proximity of the cyst to the hypothalamic-pituitary area. A total of 30 patients (17 boys) with cyst diagnosed at 4.3 ± 1 years were routinely evaluated at 5.4 ± 1 years; 24 of them had one or multiple cyst derivations. Some 23 cases had an abnormal height, weight or puberty: short (〈−2SD, 5 cases) or tall (〉2SD, 10 cases) stature, overweight (body mass index, BMI, 〉2SD, 6 cases), central precocious puberty (10 cases) and/or no progression of pubertal development (3 cases). The growth hormone (GH) peaks after pharmacological stimulation test were low (〈10 μg/l) in 16 patients, confirmed by a second evaluation in 8/11 of them. The plasma free thyroxine was low in five patients, prolactin was high in two and the cortisol and concomitant plasma and urinary osmolalities were normal. BMI was correlated negatively with the GH peaks (r=−0.37, P 〈 0.01) and positively with the plasma leptin concentrations (r=0.55, P 〈 0.01). The plasma fasting insulin concentrations were also correlated negatively with the GH peaks (r=−0.55, P 〈 0.02) and positively with the plasma insulin-like growth factor I concentrations (r=0.64, P 〈 0.002). The adult height (12 cases) was at 4SD in 1 and 〈−2SD in 4 patients, two of whom had precocious puberty untreated with gonadotropin releasing hormone (GnRH) analogue, and two had untreated GH deficiency. The adult height of those treated was normal. One girl had primary amenorrhoea and two boys had low plasma testosterone, despite a normal gonadotropin response to a GnRH test. Conclusion Suprasellar arachnoid cysts may cause deficiencies of growth hormone and thyrotropin, stimulation of the hypothalamic-pituitary-gonadal axis, tall stature and/or overweight. These last two disorders may be due to hyperinsulinism, itself due to suprasellar arachnoid cyst.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310051285
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  • 4
    Electronic Resource
    Electronic Resource
    IGF and Insulin Action in the Mammary Gland: Lessons from Transgenic and Knockout Models (2000)
    Springer
    Journal of mammary gland biology and neoplasia 5 (2000), S. 19-30 
    Details
    ISSN: 1573-7039
    Keywords: Insulin ; transgenic ; knockout ; mammary ; IGF
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Transgenic and knockout mice have become valuable experimental systems with which tostudy specific molecular events within the mammary gland of an intact animal. These modelshave provided a wealth of information about the effects of a number of oncogenes and growthfactors. This review focuses on results obtained from the application of transgenic and knockoutmodels to determine the roles of insulin and insulin-like growth factors (IGF)3 in the regulationof mammary gland development, lactation and tumorigenesis. Transgenic models whichoverexpress IGF-I or -II display specific alterations in mammary gland development and an increasedincidence of mammary tumors. Analysis of mammary gland development in knockout micewhich are deficient in IGF-I or the IGF-I receptor supports the conclusion that the IGF systemis important for normal mammary gland development. This review discusses these observationsin detail and attempts to fit them into a larger picture of IGF and insulin action in themammary gland.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009559014703
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  • 5
    Electronic Resource
    Electronic Resource
    Nitric Oxide, Superoxide, and Peroxynitrite Effects on the Insulin Secretion and Viability of βTC3 Cells (2000)
    Springer
    Annals of biomedical engineering 28 (2000), S. 102-109 
    Details
    ISSN: 1573-9686
    Keywords: Nitric oxide ; Superoxide ; Pancreatic cells ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract The onset of insulin-dependent diabetes mellitus (IDDM) is often associated with the infiltration of pancreatic cells by macrophages. Upon activation, macrophages release nitric oxide (NO) and superoxide (O 2 - ). These species or their reactive intermediates can be cytoxic, mutagenic, or carcinogenic. Previous studies have reported both positive and negative effects of extracellularly generated NO on insulin secretion and viability of pancreatic cells. Inherent problems of several previous studies assessing the effects of NO on insulin secretion include unsteady state NO concentration exposures and the generation of other potentially damaging species. In this study, these problems were eliminated by using a modified experimental system in which NO delivery was achieved via diffusion across a gas-permeable tube and O 2 - delivery was maintained using an enzymatic reaction. The delivery rates were constant, leading to steady state concentrations of NO and O 2 - in the experimental system. Based on reaction kinetics, a model was developed to predict NO, O 2 - and peroxynitrite ONOO- concentrations during the experiment. This study showed that NO, O 2 - and ONOO- at predicted concentrations as high as 2.8 μM, 0.25 μM, and 0.1 nM, respectively, do not affect the insulin secretion rates of βTC3 pancreatic cells over short times. © 2000 Biomedical Engineering Society. PAC00: 8717-d
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1114/1.258
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  • 6
    Electronic Resource
    Electronic Resource
    Bayesian Identification of a Population Compartmental Model of C-Peptide Kinetics (2000)
    Springer
    Annals of biomedical engineering 28 (2000), S. 812-823 
    Details
    ISSN: 1573-9686
    Keywords: C-peptide ; Population model ; Compartmental model ; Bayes estimation ; Markov chain Monte Carlo ; Insulin ; System identification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract When models are used to measure or predict physiological variables and parameters in a given individual, the experiments needed are often complex and costly. A valuable solution for improving their cost effectiveness is represented by population models. A widely used population model in insulin secretion studies is the one proposed by Van Cauter et al. (Diabetes 41:368–377, 1992), which determines the parameters of the two compartment model of C-peptide kinetics in a given individual from the knowledge of his/her age, sex, body surface area, and health condition (i.e., normal, obese, diabetic). This population model was identified from the data of a large training set (more than 200 subjects) via a deterministic approach. This approach, while sound in terms of providing a point estimate of C-peptide kinetic parameters in a given individual, does not provide a measure of their precision. In this paper, by employing the same training set of Van Cauter et al., we show that the identification of the population model into a Bayesian framework (by using Markov chain Monte Carlo) allows, at the individual level, the estimation of point values of the C-peptide kinetic parameters together with their precision. A successful application of the methodology is illustrated in the estimation of C-peptide kinetic parameters of seven subjects (not belonging to the training set used for the identification of the population model) for which reference values were available thanks to an independent identification experiment. © 2000 Biomedical Engineering Society. PAC00: 8715Aa, 0250Ga, 8714-g
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1114/1.1289459
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  • 7
    Electronic Resource
    Electronic Resource
    Muscle glycogen resynthesis rate in humans after supplementation of drinks containing carbohydrates with low and high molecular masses (2000)
    Springer
    European journal of applied physiology 81 (2000), S. 346-351 
    Details
    ISSN: 1439-6327
    Keywords: Key words Carbohydrate ; Osmolality ; Glycogen ; Insulin ; Glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The rate of muscle glycogen synthesis during 2 and 4 h of recovery after depletion by exercise was studied using two energy equivalent carbohydrate drinks, one containing a polyglucoside with a mean molecular mass of 500 000–700 000 (C drink), and one containing monomers and oligomers of glucose with a mean molecular mass of approximately 500 (G drink). The osmolality was 84 and 350 mosmol · l−1, respectively. A group of 13 healthy well-trained men ingested the drinks after glycogen depleting exercise, one drink at each test occasion. The total amount of carbohydrates consumed was 300 g (4.2 g · kg−1) body mass given as 75 g in 500 ml water immediately after exercise and again 30, 60 ad 90-min post exercise. Blood glucose and insulin concentrations were recorded at rest and every 30 min throughout the 4-h recovery period. Muscle biopsies were obtained at the end of exercise and after 2 and 4 h of recovery. Mean muscle glycogen contents after exercise were 52.9 (SD 27.4) mmol glycosyl units · kg−1 (dry mass) in the C group and 58.3 (SD 35.4) mmol glycosyl units · kg−1 (dry mass) in the G group. Mean glycogen synthesis rate was significantly higher during the initial 2 h for the C drink compared to the G drink: 50.2 (SD 13.7) mmol · kg−1 (dry mass) · h−1 in the C group and 29.9 (SD 12.5) mmol · kg−1 (dry mass) · h−1 in the G group. During the last 2 h the mean synthesis rate was 18.8 (SD 33.3) and 23.3 (SD 22.4) mmol · kg−1 (dry mass) · h−1 in the C and G group, respectively (n.s.). Mean blood glucose and insulin concentrations did not differ between the two drinks. Our data indicted that the osmolality of the carbohydrate drink may influence the rate of resynthesis of glycogen in muscle after its depletion by exercise.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004210050053
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  • 8
    Electronic Resource
    Electronic Resource
    Insulin alters cardiac muscle creatine kinase activity (2000)
    Springer
    Heart and vessels 15 (2000), S. 23-29 
    Details
    ISSN: 1615-2573
    Keywords: Key words Creatine kinase isoenzyme ; Insulin ; Atenolol ; Diabetes mellitus ; Myocardium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The expression of mRNAs of creatine kinase (CK)-B and CK-M has been show to be affected by insulin, and myocardial CK-MB activity is suppressed in insulin-deficient rats. We investigated the dose-related effect of insulin on CK-MB activity in cardiac and skeletal muscles. Male Wistar rats were divided into three groups: (1) control group, (2) diabetic group, injected with 65 mg/kg streptozotocin for 4 weeks, and (3) atenolol group, administered 30 mg/kg per day atenolol. Each group was further divided into three subgroups and administered either saline, or 20 (Ins 20) or 30 (Ins 30) U/kg per day insulin. After 3 weeks, the isoenzyme activity of CK and lactate dehydrogenase (LDH) in the left ventricle of the heart (LV) and the major pectoral muscle (PM) was measured. Serum insulin increased and plasma glucose decreased in Ins 20 and Ins 30, dose-dependently, in all three groups. Both CK-MB and -BB activity in LV increased dose-dependently with insulin treatment in the control, diabetes, and atenolol groups, although these changes did not occur in skeletal muscles. CK-MB in LV correlated with the serum insulin levels in all rats, while no correlation was found in the skeletal muscles. These findings suggest that insulin possibly regulates the distribution of CK isoenzymes in rat heart muscle, and that the effect of insulin is not due to the sympathetic drive induced by hypoglycemia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003800070044
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  • 9
    Electronic Resource
    Electronic Resource
    The autumnal fattening of the long-distance migratory garden warbler (Sylvia borin) is stimulated by intermittent fasting (2000)
    Springer
    Journal of comparative physiology 170 (2000), S. 627-631 
    Details
    ISSN: 1432-136X
    Keywords: Key words Fattening ; Food availability ; Insulin ; Glucagon ; Corticosterone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract To investigate the proximate influence of a changing food availability on the seasonal fattening of migratory birds, garden warblers (Sylvia borin) following postnuptial moult were food restricted once a week. Body mass, food intake, plasma hormone and metabolite levels were measured and compared to birds which always had ad libitum food access. The food-restricted birds increased their body mass significantly earlier than the controls. The accelerated fattening was initially not accompanied by hyperphagia and may be due to either an increased food utilisation efficiency or a reduced metabolic rate. An increase of basal glucagon and corticosterone and a decrease of insulin levels prior to fattening were not significant, however, they resulted in a significant decrease of the insulin:glucagon ratio. This ratio was also lower in food-restricted birds than in control birds and may account for the difference in the fattening progress. We conclude that seasonal fattening may be stimulated by a catabolic impulse which could be imposed in free-living birds by a decrease of food availability and/or by an increase of energy expenditure. A negative energy balance is hypothesised to be a common proximate factor affecting migratory as well as winter fattening.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003600000143
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  • 10
    Electronic Resource
    Electronic Resource
    Erfassung von Neurotransmitterinteraktionen mit PET und SPECT durch pharmakologische Challenge-Paradigmen (2000)
    Springer
    Der Nervenarzt 71 (2000), S. 9-18 
    Details
    ISSN: 1433-0407
    Keywords: Schlüsselwörter PET ; SPECT ; Neurotransmitter ; Interaktionen ; Psychopharmakologie ; Key words PET ; SPECT ; Neurotransmitter ; Interactions ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Functional brain imaging with positron emission tomography (PET) and single photon emission computerized tomography (SPECT) enables the in vivo study of specific neurochemical processes in the context of normal regulatory mechanisms and pathophysiological alterations of the brain. By combining these methods with pharmacological challenge-paradigms, the study of functional interactions of different neurotransmitter systems is possible. This review will present data from animal and healthy volunteer studies as well as first data from investigations in different patient populations with regard to this research direction. Especially, interactions of different neurotransmitter systems with the dopaminergic and the cholinergic system will be discussed. The database acquired so far confirms existing models of neuronal feedback -circuits, and the first clinical results are consistent with the hypothesis of an increased dopaminergic responsivity in schizophrenic patients. These results open up new perspectives for a further evaluation of treatment response predictors from drug -challenge studies and for the development of new drug treatments for neuropsychiatric disorders.
    Notes: Zusammenfassung Positronenemissionstomographie (PET) und Single Photonenemissionscomputertomographie (SPECT) ermöglichen als funktionelle bildgebende Verfahren die In-vivo-Untersuchung von spezifischen neurochemischen Prozessen im Zusammenhang mit physiologischen Regulationsvorgängen und pathophysiologischen Veränderungen des Gehirns. Durch die Kombination mit pharmakologischen Challenge-Paradigmen kann auf dieser methodischen Grundlage auch den funktionellen Interaktionen zwischen Neurotransmittersystemen nachgegangen werden. In dem vorliegenden Übersichtsartikel werden unter dieser Fragestellung durchgeführte tierexperimentelle Studien, Untersuchungen bei gesunden Probanden sowie klinische Ergebnisse dargestellt. Insbesondere der vielfältige Einfluss auf das dopaminerge und das cholinerge System wird dabei näher betrachtet. Die gewonnenen Daten bestätigen existierende Modelle von neuronalen Feedback-Regelkreisen. Erste klinische Resultate sind konsistent mit Hypothesen einer verstärkten dopaminergen Response bei schizophrenen Patienten. Die bisherigen Ergebnisse eröffnen eine Perspektive für die Entwicklung neuer Strategien zur Therapie neuropsychiatrischer Erkrankungen und bereiten zugleich den Boden für weitere Untersuchungen zur prädiktiven Bedeutung einer Challenge-Antwort bezüglich eines nachfolgenden Therapieerfolgs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001150050002
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  • 11
    Electronic Resource
    Electronic Resource
    Nutrient-dependent distribution of insulin and glucokinase immunoreactivities in rat pancreatic beta cells (1999)
    Springer
    Virchows Archiv 434 (1999), S. 75-82 
    Details
    ISSN: 1432-2307
    Keywords: Key words Rat ; Pancreatic beta cell ; Insulin ; GLUT2 glucose transporter ; Glucokinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Functional heterogeneity among pancreatic beta cells is a characteristic feature of the islets of Langerhans. Under physiological conditions, beta cells in the pancreas of fed rats exhibited heterogeneous immunohistochemical staining for insulin and glucokinase. Intracellular beta cell glucokinase staining was either faint or dense. In the pericapillary space beta cell glucokinase immunoreactivity had a polar orientation, with the highest density in cytoplasmic regions close to the blood vessels. Starvation resulted in a loss of heterogeneity with homogeneous insulin staining in all beta cells of the islets, and this was accompanied by a loss of heterogeneous glucokinase staining. The intracellular polarity of glucokinase staining in contact to blood vessels also disappeared after starvation. Refeeding resulted in the reappearance of intercellular heterogeneity. In dependence on the functional demand, the endocrine pancreas recruited insulin from beta cells according to a well-defined hierarchy, with an initial preferential mobilization of medullary beta cells. In the course of this process intracellular polarity of glucokinase staining reappeared in areas of the beta cell with functional contact to the GLUT2 glucose transporter in the plasma membrane. This can be regarded as the morphological correlate of an activation of the glucose signal recognition apparatus. Interestingly, the study also provides evidence that the changes in glucokinase distribution apparently preceded those in insulin distribution, which is in keeping with the central role of glucokinase as the glucose sensor of the pancreatic beta cell.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050308
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  • 12
    Electronic Resource
    Electronic Resource
    Effects of combination of insulin and acarbose compared with insulin and gliclazide in type 2 diabetic patients (1999)
    Springer
    Acta diabetologica 36 (1999), S. 93-97 
    Details
    ISSN: 1432-5233
    Keywords: Key words Type 2 diabetes mellitus ; Insulin ; Acarbose ; Gliclazide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this prospective study we aimed to compare insulin plus acarbose with insulin plus gliclazide with respect to their effect on insulin requirement, lipid profiles and body mass index (BMI) while achieving good glycemic control. Forty patients with type 2 diabetes mellitus who were on conventional insulin therapy (subcutaneous insulin therapy consisting of regular and NPH insulin, two times a day) were included in the study. They were randomized to double blind treatment with insulin in combination with gliclazide or acarbose for 6 months. For both groups, acceptable glycemic control was achieved at the end of study period. The mean HbA1c levels decreased from 8.32±0.26 to 7.13±0.18% in acarbose group and 8.6±0.15 to 7.48±0.21% in the gliclazide group. The difference between groups was not significant (P 0.29). In the acarbose group, total cholesterol and LDL concentration decreased significantly while other parameters did not change. In the gliclazide group, HDL levels decreased significantly from 46.6±2.48 mg/dl to 41.3±2.09 mg/dl (P 0.001) BMI increased significantly from 27.60±1.21 kg/m2 to 28.69±1.26 kg/m2. (P 0.003) Total daily insulin dose was not changed in the acarbose group significantly, but increased from 42.6±2.73 to 49.27±3.58 U/day, which was significant in gliclazide group of (P 0.016). In the acarbose group, there were no significant differences between responders and nonresponders with respect to fasting and stimulated C-peptide, HbA1c levels and baseline BMI values. But in the gliclazide group, baseline BMI values were significantly higher in the nonresponding group compared to responders (P 0.02). In conclusion, combination of insulin with acarbose can be a good alternative for type 2 diabetic patients on insulin therapy; seems more beneficial than combination with gliclazide; may have advantage of achieving good glycemic control without increasing insulin dose and BMI; also may have the advantage of providing a decrease in LDL level, which are all important to prevent atherosclerosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005920050151
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  • 13
    Electronic Resource
    Electronic Resource
    Increased glucagon-stimulated insulin secretion of cryopreserved rat islets transplanted into nude mice (1999)
    Springer
    Journal of molecular medicine 77 (1999), S. 107-110 
    Details
    ISSN: 1432-1440
    Keywords: Key words Pancreatic islet transplantation ; Cryopreservation ; Conservation ; Insulin ; Nude mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cryopreservation is the only available technique for long-term storage of pancreatic islets. The freezing/thawing protocol may cause considerable loss of viable islet tissue and impair its function in vivo. The aim of this study was to investigate glucose and insulin levels after transplantation of fresh and cryo/thawed rat islets. Rat pancreatic islets were isolated following intraductal collagenase injection and Ficoll gradient purification. After isolation, islets were cultured for 24 h and then either transplanted or frozen after stepwise addition of DMSO according to Rajotte et al. and stored in liquid nitrogen. After rapid thawing islets were stepwise transferred into RPMI medium and cultured for another 24 h. The recipients were athymic mice with streptozotocine-induced diabetes. Two hundred fresh (n=13) or cryo/thawed (n=15) islets were transplanted beneath the renal capsule. Glucose levels were measured for 14 days and blood samples for insulin determination were obtained 15 min after i.p. glucagon (10 mg/kg) administration on day 14. Glucose levels were normalized (〈9 mmol/l) in all recipients within 3 days since transplantation. On day 14, mean fasting values±SE in fresh and cryo/thawed islet groups were 4.0±0.6 and 4.4±0.4 mmol/l, respectively (P〉0.05). Fasting insulin levels were higher in the cryo/thaw than in the fresh islet group (1.67±0.33 vs 0.57±0.13 ng/ml; P〈0.01). Post-glucagon levels did not differ significantly (1.45±0.24 vs 0.86±0.24 ng/ml; P=0.06). While glucagon significantly increased insulin levels (P〈0.01) in the fresh islet group, no change in insulin levels was observed (P〉0.05) in the cryo/thaw group. Immunohistochemical staining demonstrated fragmentation of viable islet tissue which was more apparent in the cryo/thaw group. We conclude that in a short-term study cryo/thawed rat islets produce higher insulin levels than fresh islets transplanted into nude mice. This may be due to better islet survival or loss of feed-back regulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001090050313
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  • 14
    Electronic Resource
    Electronic Resource
    Nachbarschaft von Tic und Zwang (1999)
    Springer
    Der Nervenarzt 70 (1999), S. 1-10 
    Details
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Tic-Störung ; Zwangsstörung ; Kinder ; Jugendliche ; Neurobiologie ; Psycho- pharmakologie ; Verhaltenstherapie ; Key words Tic-disorder ; Obsessive-compulsive disorder ; Children ; Adolescents ; Neurobiology ; Psychopharmacology ; Behavior therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In children and adolescents motor/vocal tics and obsessive-compulsive behavior are known to be closely related. Thereby, a continuum of symptoms ranging from single tics to a mixed picture of tics/rituals/obsessive-compulsive traits to clinically relevant obsessions and compulsions could be described. As neurobiological substrates dysfunctions in corresponding cortico-striato-thalamo-cortical circuits (sensorimotor circuit in tic symptomatology, orbitofrontal circuit in obsessive-compulsive behavior) were postulated. For both disturbances behavioral therapy can be used to improve control mechanisms to counterregulate tics and obsessive-compulsive behavior, respectively, and psychopharmacological agents can be administerd to compensate dysbalances in neurotransmitter systems. In case of a mixed symptomatologic picture it is necessary to include interventions for both pols of the symptom-continuum in the therapeutic programme to achieve extensive improvement as a basis for a further positive development of the patient.
    Notes: Zusammenfassung Motorische/vokale Tics und zwanghafte Verhaltensweisen kommen bei Kindern und Jugendlichen häufig gemeinsam vor; dabei kann ein Symptomkontinuum von solitär auftretenden Tics über ein Mischbild von Tics und Ritualen/zwanghaften Gedanken und/oder Handlungen bis hin zu eindeutigen Zwangsphänomenen beschrieben werden. Neurobiologisch können diesem Symptomkontinuum unterschiedlich ausgebreitete Dysfunktionen entsprechender kortiko-striato-pallido-thalamo-kortikaler Regulationssysteme zugrunde liegen. Therapeutisch lassen sich bei beiden Verhaltensauffälligkeiten mittels verhaltenstherapeutischer Techniken Steuerungs- und Kontrollmöglichkeiten zur Gegenregulation der Auffälligkeiten verbessern sowie durch Einsatz von Psychopharmaka Dysbalancen von Neurotransmittersystemen ausgleichen. Bei einem Mischbild von Tics und Zwängen sind therapeutische Interventionen für beide Zielbereiche erforderlich. Nur so können umfassende Verbesserungen erreicht und günstige Entwicklungsbedingungen für die betroffenen Kinder und Jugendlichen eröffnet werden.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001150050394
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  • 15
    Electronic Resource
    Electronic Resource
    Gene transfer into insect brain and cell-specific expression of bombyxin gene (1999)
    Springer
    Development genes and evolution 209 (1999), S. 447-450 
    Details
    ISSN: 1432-041X
    Keywords: Key words Bombyxin ; Insulin ; Bombyx mori ; Electroporation ; Cell-specific expression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  A transgene reporter consisting of the bombyxin gene promoter and the green fluorescent protein coding region was introduced into intact brains of the silkworm Bombyx mori by in vitro electroporation. After in vitro culture of the brains, the fluorescence derived from the introduced reporter gene was observed in all cases in eight neurosecretory cells that had previously been identified as bombyxin-producing cells (BPCs). Although the fluorescence was not always observed in all cells, it was specific to BPCs, indicating that the reporter was under the control of the bombyxin gene promoter in a BPC-specific manner. Electroporatical introduction of a reporter gene was therefore found to be a suitable method for analyzing cell-specific expression in intact tissues and to be substitute for germ-line transmission of reporters in the transgenic system. Application of this technique enables us to analyze the cell-specific expression of transgene reporters within a few days and treat more than several dozens of the reporters within 1 month, which is difficult to do with the transgenic system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004270050277
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  • 16
    Electronic Resource
    Electronic Resource
    Beyond discounting: possible experimental models of impulse control (1999)
    Springer
    Psychopharmacology 146 (1999), S. 339-347 
    Details
    ISSN: 1432-2072
    Keywords: Key words Hyperbolic discounting ; Impulsivity ; Self-control ; Reward bundling ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Animal studies of impulsivity have typically used one of three models: a delay of reward procedure, a differential reinforcement for low rate responding (DRL) procedure, or an autoshaping procedure. In each of these paradigms, we argue, measurement of impulsivity is implicitly or explicitly equated with the effect delay has on the value of reward. The steepness by which delay diminishes value (the temporal discount function) is treated as an index of impulsivity. In order to provide a better analog of human impulsivity, this model needs to be expanded to include the converse of impulsivity – self-control. Through mechanisms such as committing to long range interests before the onset of temptation, or through bundling individual choices into classes of choices that are made at once, human decision-making can often look far less myopic than single trial experiments predict. For people, impulsive behavior may be more often the result of the breakdown of self-control mechanisms than of steep discount functions. Existing animal models of self-control are discussed, and future directions are suggested for psychopharmacological research.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00005480
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  • 17
    Electronic Resource
    Electronic Resource
    Insulin modulation of ATP-sensitive K+ channel of rat skeletal muscle is impaired in the hypokalaemic state (1999)
    Springer
    Pflügers Archiv 437 (1999), S. 235-240 
    Details
    ISSN: 1432-2013
    Keywords: Key words Hypokalaemic periodic paralysis ; ATP-sensitive K+ channels ; Insulin ; Skeletal muscle ; Patch clamp
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In the present work, we examined the effects of in vivo administration of insulin to rats made hypokalaemic by feeding a K+-free diet. The i.p. injection of insulin in the hypokalaemic rats provoked muscle paralysis within 3–5 h. Consistent with this observation, the skeletal muscle fibres of the paralysed rats were depolarized. In contrast, in the normokalaemic animals, insulin neither provoked paralysis nor produced significant fibre hyperpolarization. In the hypokalaemic rats, insulin almost completely abolished the sarcolemma adenosine triphosphate (ATP)-sensitive K+ currents without altering the sensitivity of the channels to ATP or glibenclamide. In contrast, in the normokalaemic rats, insulin enhanced ATP-sensitive K+ currents that became also resistant to ATP and glibenclamide. Our experiments indicate that the modulation of the sarcolemma ATP-sensitive K+ channels by insulin is impaired in the hypokalaemic state. This phenomenon appears to be related to the fibre depolarization and paralysis observed in the same animals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050774
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  • 18
    Electronic Resource
    Electronic Resource
    Interleukin-1β-induced nitric oxide synthesis in aortic rings from normal and hyperinsulinaemic rats: effect of physical exercise (1999)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 360 (1999), S. 63-68 
    Details
    ISSN: 1432-1912
    Keywords: Key words Arterial smooth muscle ; Glucose ; Inducible NO synthesis ; Insulin ; Lean and obese Zucker rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Insulin has been suggested to prevent the induction of nitric oxide synthase (NOS) in vitro in arterial smooth muscle, but whether such a mechanism is operative in vivo is not known. Therefore, we evaluated the sensitivity of smooth muscle NOS to induction by interleukin-1β (IL-1β) in aortic rings of lean and obese Zucker rats, a model of experimental hyperinsulinaemia. In order to modulate the insulin and glucose balance of the rats, a 22-week-long treadmill exercise was included in the study. The training attenuated weight gain and reduced blood glucose in the obese and lean rats, whereas the abnormally high plasma insulin of the obese rats remained unaffected. A 6-h incubation of aortic rings with IL-1β (10 ng/ml) increased cyclic GMP in smooth muscle by approximately threefold in all groups, and this effect was prevented by methylene blue. The contractile sensitivity of endothelium-denuded aortic rings to phenylephrine was reduced by incubation with IL-1β (1 ng/ml and 10 ng/ml) in the exercised obese and lean rats, whereas no significant change was observed in the sedentary groups. The aortic maximal contractile force induced by phenylephrine was reduced in sedentary and exercised obese rats by incubation with IL-1β, while no change was detected in the lean rats. The aortic relaxation to exogenous L-arginine was augmented by IL-1β in all groups, while the relaxation sensitivity to L-arginine after induction by IL-1β was enhanced by exercise in the obese but not in the lean rats. Finally, the relaxation to nitroprusside was not significantly affected by IL-1β in any of the study groups. In conclusion, since maximal contractile force generation to phenylephrine was reduced by IL-1β in the obese but not in the lean rats, the sensitivity of NOS to induction by IL-1β was higher in arterial smooth muscle of the obese than the lean Zucker rats. Thus, this model of hyperinsulinaemia was not associated with reduced sensitivity of smooth muscle NOS to induction by IL-1β. Regular exercise did not change plasma insulin concentrations, but it enhanced the action of insulin in both strains as reflected by reduced blood glucose, and increased the sensitivity of smooth muscle NOS to induction by IL-1β.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002109900036
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  • 19
    Electronic Resource
    Electronic Resource
    Forskolin increases apical sodium conductance in cultured toad kidney cells (A6) by stimulating membrane insertion (1999)
    Springer
    Pflügers Archiv 438 (1999), S. 195-204 
    Details
    ISSN: 1432-2013
    Keywords: Key words A6 cells ; Capacitance ; Hormones ; Insulin ; Membrane area ; Membrane traffic ; Renal epithelia ; Water permeability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The role of membrane traffic in the stimulation of apical Na+ permeability caused by increases in cytoplasmic cyclic AMP was assessed by measuring the effects of forskolin on transepithelial capacitance (C T), transepithelial conductance (G T), and short-circuit current (I sc) in A6 cultured toad kidney cells. Apical water permeability was probed by recording cell volume changes after reducing the osmolality of the apical bath. We found that forskolin does not increase the osmotic water permeability of the apical membrane of A6 cells, and thus does not stimulate the insertion of water channels. Comparison of the effects of forskolin and insulin on Na+ transport demonstrated that both agents produce reversible increases in C T, G T and I sc. G T and C T increased proportionally during the rising phase of the insulin response. However, a non-linear relationship between both parameters was recorded when forskolin was given in NaCl Ringer’s solution. The relationship between C T and G T became linear after the effects of forskolin on Cl– conductances were eliminated by substituting Cl– by an impermeant anion. In contrast, in Cl–-containing Na+-free solutions, the non-linearity became more pronounced. Successive additions of insulin and forskolin caused additive increases in C T. Because increases in C T and Na+ transport occurred in the absence of stimulation of water permeability and increases of C T and G T were directly proportional when Na+ was the major permeating ion across the apical membrane, we suggest that the increase in apical Na+ permeability in the presence of either forskolin or insulin is due to the insertion of channels residing in intracellular pools. In contrast, the increased Cl– permeability caused by forskolin may be related to the activation of channels already present in the membrane.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050898
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  • 20
    Electronic Resource
    Electronic Resource
    Metabolic and ultrastructural effects of cyclosporin A on pancreatic islets (1999)
    Springer
    Transplant international 12 (1999), S. 208-212 
    Details
    ISSN: 1432-2277
    Keywords: Key words Cyclosporin A ; Langerhans ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated the effect of different doses of cyclosporin A (CyA) on glucose and insulin levels, as well as its residual effects on pancreatic islets ultrastructure after discontinuation of the drug. We studied four groups of Wistar rats. One control- (n = 5) and three experimental groups, n = 10 each, were treated with different doses of CyA IM for 14 days: group I, 5 mg/Kg; group II, 15 mg/Kg; and group III, 25 mg/Kg. Five animals of each group were sacrificed after 14 days, and the remaining five after 21 days to assess residual CyA effects. On the day of sacrifice, the rats underwent maltose absorption test, and glucose and insulin levels were measured. Pancreatic biopsies were obtained on day 21 to evaluate islets ultrastructure by electron microscopy. As a result, statistically significant, dose dependent (P 〈 0.05) increases in glucose and insulin levels were observed in CyA-treated groups. Groups II and III showed insulin levels significantly higher after fasting (P 〈 0.05) on day 14 comparing to the controls, while in groups I and II values returned to normal after CyA discontinuation. Group III showed persistently increased insulin levels on day 21. Pancreatic ultrastructural changes were observed only in group III. We can conclude that CyA effects on glucose and insulin levels were temporary and reversible at low doses. Ultrastuctural changes in the pancreatic islets may occur with high doses of CyA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050212
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  • 21
    Electronic Resource
    Electronic Resource
    Insulin-induzierte Hypoglycaemia factitia aus diätetischen Gründen (1999)
    Springer
    Rechtsmedizin 9 (1999), S. 190-192 
    Details
    ISSN: 1434-5196
    Keywords: Key words Hypoglycaemia factitia ; Insulin ; Diet ; Lethal outcome ; Schlüsselwörter Hypoglykaemia factitia ; Insulin ; Diät ; Tödlicher Verlauf
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Description / Table of Contents: Zusammenfassung Wir berichten über den Fall einer 28jährigen, nicht insulinpflichtigen nicht-Diabetikerin, in deren Anamnese eine hypoglykaemische Episode vor dem Todeseintritt bekannt wurde. Autoptisch wurde eine (heimliche) Applikation von Insulin durch letal hohe Insulinspiegel im zentralen und peripheren Blut mit Hypoglykaemie diagnostiziert. Nach der Anamnese, den Ergebnissen des Ermittlungsverfahrens und der Autopsie konnte die Applikation von Insulin aus suizidaler und homizidaler Absicht oder im Rahmen eines Münchhausen-Syndroms ausgeschlossen werden. Vielmehr handelte es sich in der Gesamtschau um eine Hypoglykaemia factitia aus diätetischen Gründen.
    Notes: Abstract The medical history of a 28-year-old non-insulin-dependent and non-diabetic patient with a hypoglycaemic episode before death is reported. At autopsy, an (surreptious) insulin administration was documented by lethally high serum insulin in central and peripheral blood during hypoglycaemia, According to the anamnesis, the judical inquiry and the autopsy findings, a suicidal intent, murder by insulin or Munchhausen-syndrome could be excluded. We therefore diagnosed a hypoglycaemia factitia caused by the diet.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001940050107
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  • 22
    Electronic Resource
    Electronic Resource
    Effect of moderate physical activity on plasma leptin concentration in humans (1999)
    Springer
    European journal of applied physiology 79 (1999), S. 331-335 
    Details
    ISSN: 1439-6327
    Keywords: Key words Leptin ; Exercise Energy balance ; Insulin ; Glucocorticoids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In subjects who maintain a constant body mass, the increased energy expenditure induced by exercise must be compensated by a similar increase in energy intake. Since leptin has been shown to decrease food intake in animals, it can be expected that physical exercise would increase energy intake by lowering plasma leptin concentrations. This effect may be secondary either to exercise-induced negative energy balance or to other effects of exercise. To delineate the effects of moderate physical activity on plasma leptin concentrations, 11 healthy lean subjects (4 men, 7 women) were studied on three occasions over 3 days; in study 1 they consumed an isoenergetic diet (1.3 times resting energy expenditure) over 3 days with no physical activity; in study 2 the subjects received the same diet as in study 1, but they exercised twice daily during the 3 days (cycling at 60 W for 30 min); in study 3 the subjects exercised twice daily during the 3 days, and their energy intake was increased by 18% to cover the extra energy expenditure induced by the physical activity. Fasting plasma leptin concentration (measured on the morning of day 4) was unaltered by exercise [8.64 (SEM 2.22) 7.17 (SEM 1.66), 7.33 (SEM 1.72) 1μg · l−1 in studies 1, 2 and 3, respectively]. It was concluded that a moderate physical activity performed over a 3-day period does not alter plasma leptin concentrations, even when energy balance is slightly negative. This argues against a direct effect of physical exercise on plasma leptin concentrations, when body composition is unaltered.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004210050516
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  • 23
    Electronic Resource
    Electronic Resource
    Genome-wide scanning for type 2 diabetes susceptibility in Canadian Oji-Cree, using 190 microsatellite markers (1999)
    Springer
    Journal of human genetics 44 (1999), S. 10-14 
    Details
    ISSN: 1435-232X
    Keywords: Key words Complex disease ; Carbohydrate ; Insulin ; Aboriginal populations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We undertook a genome-wide scan using 190 markers with an average separation of 20 cM in 49 Canadian Oji-Cree sib pairs affected with type 2 diabetes. Four of these markers, one each on chromosomes 6, 8, 16, and 22, showed both suggestive linkage and suggestive association with type 2 diabetes in the Oji-Cree. None of these markers corresponded to any chromosomal region or marker that has so far been linked with type 2 diabetes in other populations. Thus, there might be several genetic loci that confer susceptibility to type 2 diabetes in this study sample. We are following up on these preliminary leads by increasing the density of the markers within these linked and associated regions, and also by increasing the number of study subjects. Also, we found instances in which there were wide disparities between the Oji-Cree and reference Caucasians with respect to marker heterozygosity. This suggests that a particular set of markers for genome-wide scanning will have different informativeness in different ethnic groups. Thus, different marker sets will likely be required for different ethnic groups in order to maximize their information content for linkage calculations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s100380050097
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  • 24
    Electronic Resource
    Electronic Resource
    The effect of euglucaemic hyperinsulinaemia on forearm blood flow and glucose uptake in the human forearm (1998)
    Springer
    Acta diabetologica 35 (1998), S. 203-206 
    Details
    ISSN: 1432-5233
    Keywords: Key words Glucose ; Insulin ; Hyperinsulinaemia ; Blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Insulin-mediated stimulation of blood flow to skeletal muscle has been proposed to be of major importance for insulin-mediated glucose uptake. The aim of this study was to investigate the relative importance of blood flow and glucose extraction as determinants of insulin-mediated glucose uptake in the human forearm. Forearm blood flow (FBF), glucose extraction and oxygen consumption were evaluated for 100 min during the euglycaemic hyperinsulinaemic clamp (92 mU/l) in nine healthy subjects. FBF was measured by venous occlusion plethysmography. Forearm glucose uptake increased sevenfold during the hyperinsulinaemia (P〈0.001). Forearm glucose extraction showed a minor increase during the first 10 min of hyperinsulinaemia, but the most marked increase took place between 10 and 20 min (+170%). Thereafter, only a minor further increase was seen. During the first 10 min of hyperinsulinaemia FBF was unchanged. Thereafter, FBF increased steadily to a plateau reached after 60 min (+50%, P〈0.001). A close relationship between whole body glucose uptake and FBF was seen at the end of the clamp (r = 0.75, P〈0.02), but at this time the relationship between whole body glucose uptake and forearm glucose extraction was not significant. The modest increase in O2 consumption seen at the beginning of the clamp (+19%) was not related to FBF during the early phase of the clamp. In conclusion, the early course of insulin-mediated glucose uptake in the human forearm was mainly due to an increase in glucose extraction. However, with time the insulin-mediated increase in blood flow increased in importance and after 100 min of hyperinsulinaemia FBF was the major determinant of glucose uptake.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005920050132
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  • 25
    Electronic Resource
    Electronic Resource
    Functioning human insulinomas (1998)
    Springer
    Virchows Archiv 433 (1998), S. 495-504 
    Details
    ISSN: 1432-2307
    Keywords: Key words Insulinomas ; Prohormone convertases ; Carboxypeptidase H ; Insulin ; Proinsulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Sixty-seven insulinomas were investigated by immunohistochemistry using site-directed antibodies against insulin, proinsulin, chromogranin A, HISL-19, and four proteins directly or indirectly involved in the proteolytic processing of proinsulin: the prohormone convertases PC2 and PC3, carboxypeptidase H (CPH) and 7B2. Results were expressed in a six-grade score according to the frequency of immunoreactive tumour cells. Insulin was expressed by all tumours, appearing in either a diffuse or a polarized pattern and being detected in more than 30% of tumour cells in all cases but three. Proinsulin was also expressed in all tumours, with more than 50% of tumour cells immunoreactive in all cases but 5. It was consistently localized in the Golgi apparatus. In about half the cases, moreover, it also showed diffuse cytoplasmic staining, usually with a very sparse distribution. Trabecular and solid insulinomas did not present specific, homogeneous patterns of insulin immunostaining. However, insulin immunoreactivity was much more abundant in trabecular than in solid neoplasms, being present in virtually all tumour cells (score 6) in 50% and 8% of cases, respectively. Virtually all insulinomas expressed PC2, PC3, CPH and 7B2, usually in 30–100% of tumour cells, with a frequency significantly related to that of insulin. However, detection of PC2 and 7B2 was slightly less frequent than that of PC3 and CPH. In consecutive sections these proteins were found to be mostly co-localized with insulin and chromogranin A but not with proinsulin. They were heavily expressed in all 10 tumours with more than 10% of cells showing cytoplasmic proinsulin immunoreactivity, indicating that the leakage of proinsulin from the Golgi compartment is not associated with faulty expression of converting enzymes and possibly reflects a saturated processing capacity. HISL-19 immunoreactivity was found in both Golgi apparatus and insulin stores, indicating that the relevant antigen is different from all other proteins investigated. These results do not support a defect in expression or localization of proinsulin-processing enzymes in most insulinomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050280
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  • 26
    Electronic Resource
    Electronic Resource
    Neuropathy in diabetic BB/Wor rats treated with insulin implants (1998)
    Springer
    Acta neuropathologica 96 (1998), S. 144-150 
    Details
    ISSN: 1432-0533
    Keywords: Key words Neuropathy ; Hypoglycaemia ; Hyperglycaemia ; Insulin ; BB/Wor rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To elucidate the pathophysiology of diabetic neuropathy many workers have examined nerve specimens from diabetic rats. While most workers found that animals with high blood glucose levels develop neuropathy, some researchers report that the peripheral nerves are normal in hyperglycaemic rats. Hypoglycaemia may also cause neuropathy. Some workers suggest that neuropathy is linked to fluctuations of the blood glucose level. In the present study we examine plantar nerves of diabetic BB/ Wor rats maintained on an eu-/hyperglycaemic or an eu-/ hypoglycaemic regime with insulin implants. Treatment with implants worked well. Light microscopic examination of nerve fibres in non-diabetic control rats and in eu-/ hyperglycaemic diabetic rats showed a normal picture. Preparations from eu-/hypoglycemic rats showed irregular myelin sheaths and signs of Wallerian degeneration. The lengths and diameters of the largest internodes were significantly subnormal. We conclude, that periodic moderate hypoglycaemia, but not periodic moderate hyperglycaemia, elicits neuropathy in diabetic BB/Wor rats treated with insulin implants.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010050874
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  • 27
    Electronic Resource
    Electronic Resource
    Hypoglycaemic neuropathy in BB/Wor rats treated with insulin implants: electron microscopic observations (1998)
    Springer
    Acta neuropathologica 96 (1998), S. 151-156 
    Details
    ISSN: 1432-0533
    Keywords: Key words Neuropathy ; Hypoglycemia ; Insulin ; implant ; Rat ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Insulin-dependent diabetes mellitus is a chronic metabolic disease that causes long-term secondary complications such as neuropathy. The occurrence of diabetic neuropathy has generally been thought of as being associated with hyperglycaemia. However, in a previous light microscopic examination of plantar nerves in diabetic BB/Wor rats treated with insulin implants we found that eu-/hyperglycaemic rats present a normal picture, whereas eu-/hypoglycaemic rats show severe changes. The aim of the present work is to supplement our previous light microscopic report with electron microsocpic data from the lateral plantar nerve of normal, eu-/hyperglycaemic and eu-/hypoglycaemic BB/Wor rats. Under the electron microscope lateral plantar nerves collected from eu-/hyperglycaemic rats presented a qualitatively normal picture. In addition, the fibre numbers and the size distribution of the myelinated fibres were normal. In contrast, specimens from eu-/hypoglycaemic BB/Wor rats showed severe qualitative changes, interpreted as signs of axonal de- and regeneration. The total number of axons was somewhat subnormal and the sizes of the myelinated fibres were strongly shifted towards smaller diameters. These data confirm our previous light microscopic observations. We conclude that eu-/hypoglycaemic BB/Wor rats treated with insulin implants, but not similarly treated eu-/hyperglycaemic animals, develop a neuropathy in their plantar nerves.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010050875
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  • 28
    Electronic Resource
    Electronic Resource
    A novel member of the bombyxin gene family: structure and expression of bombyxin G1 gene, an insulin-related peptide gene of the silkmoth Bombyx mori (1998)
    Springer
    Development genes and evolution 208 (1998), S. 407-410 
    Details
    ISSN: 1432-041X
    Keywords: Key words Bombyxin ; Insulin ; Bombyx mori ; Multigene family ; Brain neurosecretory cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  Bombyxin G1 gene, a novel insulin-related peptide gene of the silkmoth Bombyx mori, has been identified. The G1 gene encodes a precursor peptide which shows 41–56% and 28% sequence identities with preprobombyxins previously characterized and human preproinsulin, respectively. The G1 gene forms a pair with bombyxin C2 gene with opposite transcriptional orientation in a bombyxin gene cluster. The bombyxin G1 mRNA in Bombyx brain was shown to locate in four pairs of medial neurosecretory cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004270050197
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  • 29
    Electronic Resource
    Electronic Resource
    Cyclosporin A induces apoptosis in rat hepatocytes in culture (1998)
    Springer
    Archives of toxicology 72 (1998), S. 559-565 
    Details
    ISSN: 1432-0738
    Keywords: Key words Proliferation ; Epidermal growth factor (EGF) ; Insulin ; Hepatocyte ; Cyclosporin A
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cyclosporin A (CsA) at concentrations up to 1 μM induced apoptosis in a dose-dependent manner in cultured rat hepatocytes for 48 h in the presence of insulin and epidermal growth factor (EGF). The effect of CsA was evidenced by the DNA fragmentation pattern constituted by fragments of multiples of 180–200 base pairs, which is a characteristic of programmed cell death. The metabolic activity did not change significantly in the presence of 0.1 μM CsA and diminished to 49% of control in the presence of 1 μM CsA. Changes in the metabolic activity were correlated with a decrease in both [methyl-3H]thymidine uptake and DNA content, which reflects a decrease in the cell number. The treatment of cells with CsA (1 μM) decreased the metabolic activity/DNA content ratio by 24% with respect to dimethyl sulphoxide (DMSO) control, which also suggests, under these conditions, that the necrosis achieved is at most only 24%. In addition, the changes observed (apoptotic process, arrest of the cell cycle and apparition of a necrotic process) were correlated with an increase in the high-affinity guanosine triphosphatase (GTPase) enzymes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050543
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  • 30
    Electronic Resource
    Electronic Resource
    Slowly deteriorating insulin secretion and C-peptide production characterizes diabetes mellitus in infantile cystinosis (1998)
    Springer
    European journal of pediatrics 157 (1998), S. 738-742 
    Details
    ISSN: 1432-1076
    Keywords: Key words Diabetes mellitus ; Infantile cystinosis ; Insulin ; C-peptide ; Chronic renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Infantile cystinosis, a rare lysosomal storage disease of cystine, leads to Fanconi syndrome and end-stage renal failure. After renal transplantation, no recurrence of the disease occurs in the graft, but other organ involvement becomes evident later in life. Diabetes mellitus has been associated with cystinosis, but the mechanisms of impaired glucose tolerance have not yet been characterized. Here, we studied glucose tolerance, glucose constant decay (k-values), insulin and C-peptide by intravenous glucose tolerance test (IVGTT) in eight patients with infantile cystinosis (three with impaired GFR (CRF) and five after kidney transplantation (KTX)). For comparison, 15 age-matched children with CRF and 15 age-matched KTX patients were analysed. Both early and second insulin secretion phases were diminished in patients with infantile cystinosis, whereas in CRF, k-values were no different from control patients. After renal transplantation, k-values were significantly lower in cystinotic patients with a markedly reduced early insulin secretion phase. There was a significant negative correlation between k-values and age in patients with cystinosis. Repetitive IVGTTs in these patients demonstrated progressive but rather slow loss of first phase insulin secretion and C-peptide production, suggesting a slowly reducing secretion potential of the beta cell due to cystine storage. Conclusion Unlike type I diabetes mellitus, glucose intolerance in patients with infantile cystinosis is characterized by a slow, progressive loss of insulin secretion and C-peptide production. For these patients, the data indicate a 50% risk of developing glucose intolerance by the age of 18 years. We recommend to perform intravenous glucose tolerance tests at 5-year intervals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310050926
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  • 31
    Electronic Resource
    Electronic Resource
    Expression of type III hyperlipoproteinemia in patients homozygous for apolipoprotein E-2 is modulated by lipoprotein lipase and postprandial hyperinsulinemia (1998)
    Springer
    Journal of molecular medicine 76 (1998), S. 355-364 
    Details
    ISSN: 1432-1440
    Keywords: Key words Postprandial hyperlipoproteinemia ; Lipoprotein lipase ; Insulin ; Apolipoprotein E ; Hyperlipoproteinemia type III
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Type III hyperlipoproteinemia (HLP) is a multifactorial disorder associated with homozygosity for the apolipoprotein (apo) E-2 allele. Factors which may promote the development of HLP include lipoprotein lipase (LPL) and hyperinsulinemia. These factors were investigated in eight patients with type III HLP and in nine normolipidemic controls. In vitro the interaction of apoE with LPL was analyzed in cell binding assays. All type III HLP patients showed delayed triglyceride (TG) clearance and remnant lipoprotein accumulation in an oral fat tolerance test. Normolipidemic apoE-2/2 controls revealed normal TG clearance comparable to apoE3/3 controls. HLP patients showed lower LPL activity and mass than controls. Analysis of the LPL gene revealed an Asn 291→Ser mutation in three patients and a –93 T-G substitution combined with an Asp 9→Asn mutation in one control subject. In addition to LPL abnormalities, postprandial hyperinsulinemia was observed in five out of eight patients. In vitro LPL compensated the defective function of apoE-2 in mediating remnant lipoprotein binding to cells. In summary, seven out of eight patients with type III HLP showed LPL abnormalities and/or postprandial hyperinsulinemia. Together with the in vitro data these findings support a coordinate effect of apoE and LPL for the manifestation of type III HLP. Hyperinsulinemia appears to be an additional factor important for disease expression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001090050227
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  • 32
    Electronic Resource
    Electronic Resource
    Cellular regulation of islet hormone secretion by the incretin hormone glucagon-like peptide 1 (1998)
    Springer
    Pflügers Archiv 435 (1998), S. 583-594 
    Details
    ISSN: 1432-2013
    Keywords: Key words GLP-1 ; cAMP ; Insulin ; Calcium ; NIDDM ; Glucagon ; Islet ; GIP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Glucagon-like peptide 1 is a gastrointestinally derived hormone with profound effects on nutrient-induced pancreatic hormone release. GLP-1 modulates insulin, glucagon and somatostatin secretion by binding to guanine nucleotide binding protein-coupled receptors resulting in the activation of adenylate cyclase and generation of cyclic adenosine monophosphate (cAMP). In the B-cell, cAMP, via activation of protein kinase A, interacts with a plethora of signal transduction processes including ion channel activity, intracellular Ca2+ handling and exocytosis of the insulin-containing granules. The stimulatory action of GLP-1 on insulin secretion, contrary to that of the currently used hypoglycaemic sulphonylureas, is glucose dependent and requires the presence of normal or elevated concentrations of the sugar. For this reason, GLP-1 attracts much interest as a possible novel principle for the treatment of human type-2 diabetes. Here we review the actions of GLP-1 on islet cell function and attempt to integrate current knowledge into a working model for the control of pancreatic hormone secretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050558
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  • 33
    Electronic Resource
    Electronic Resource
    Insulin dominantly suppresses hepatitis B virus gene expression in cultured human hepatoma cells (1997)
    Springer
    Journal of biomedical science 4 (1997), S. 295-299 
    Details
    ISSN: 1423-0127
    Keywords: Hepatoma ; Hepatitis B surface antigen ; Insulin ; Glucocorticoid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We have shown previously that insulin suppresses the expression of hepatitis B surface antigen (HBsAg) gene from an endogenous integrated viral genome in cultured human hepatoma Hep3B cells. In this study, we demonstrated that insulin suppresses the viral mRNA transcribed from transiently transfected tandem repeat hepatitis B virus (HBV) dimer DNA or DNA fragment that contains only the major HBsAg gene. Insulin treatment also resulted in a decrease in HBV viral particles produced by the HBV-DNA-transfected cells in a dose-dependent manner. Furthermore, when insulin was simultaneously added with glucocorticoid, which stimulates HBV gene expression, the stimulatory effect of glucocorticoid was completely abolished. Our results suggest that insulin has a dominant negative effect on the HBV gene expression in cultured human liver cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02258353
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  • 34
    Electronic Resource
    Electronic Resource
    Insulin effects on ouabain binding in A6 renal cells (1997)
    Springer
    Pflügers Archiv 434 (1997), S. 11-18 
    Details
    ISSN: 1432-2013
    Keywords: Key words A6 epithelia ; Ouabain binding ; Insulin ; Cycloheximide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The effects of insulin on the Na+-K+-ATPase pump of the basolateral membrane of tight epithelia were evaluated by measuring transepithelial transport and [3H]ouabain binding in cultured A6 kidney cells. [3H]Ouabain binding in epithelia incubated in either K+-containing or K+-free solutions was measured. Insulin induced increases in transepithelial sodium transport, as measured by the short-circuit current (I sc), and in the initial rate of [3H]ouabain binding determined when the preparation was bathed in K+-containing solutions. However, when initial [3H]ouabain binding in tissues incubated in K+-free solutions was measured the stimulation of the initial rate of [3H]ouabain binding caused by insulin was markedly reduced. Incubating the apical side of the epithelium with either amiloride or Na+-free solutions also reduced or abolished the increase in the initial rate of [3H]ouabain binding caused by insulin. Equilibrium binding measurements showed that insulin did not increase the maximum number of [3H]ouabain-binding sites in tissues incubated with either normal K+ or K+-free solutions. These results indicate that the increase in the initial rate of [3H]ouabain binding under transporting conditions is due to an effect on the binding kinetics of ouabain, probably related to an increased rate of Na+ entry, rather than to an increase in the number of Na+-K+-ATPases in the basolateral membrane. Cycloheximide inhibited both the increase in I sc and the increase in the initial rate of [3H]ouabain binding caused by insulin in epithelia incubated in K+-containing solutions. However, cycloheximide was without effect on the initial rate of [3H]ouabain binding in insulin-treated tissues incubated in K+-free solution. This finding suggests that the cycloheximide-sensitive step of the action of insulin is related to Na+ delivery to the pump.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050357
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  • 35
    Electronic Resource
    Electronic Resource
    Multisite regulation of insulin secretion by cAMP-increasing agonists: evidence that glucagon-like peptide 1 and glucagon act via distinct receptors (1997)
    Springer
    Pflügers Archiv 434 (1997), S. 515-524 
    Details
    ISSN: 1432-2013
    Keywords: Key words GLP-1 ; Exocytosis ; B-cell ; Glucagon ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The mechanisms by which glucagon-like peptide 1(7–36)amide (GLP-1[7–36]amide) potentiates insulin secretion were investigated by measurements of whole-cell K+ and Ca2+ currents, membrane potential, the cytoplasmic Ca2+ concentration ([Ca2+]i) and exocytosis in mouse pancreatic B-cells. GLP-1(7–36)amide (10 nM) stimulated glucose-induced (10 mM) electrical activity in intact pancreatic islets. The effect was manifested as a 34% increase in the duration of the bursts of action potentials and a corresponding 28% shortening of the silent intervals. GLP-1(7–36)amide had no effect on the electrical activity at subthreshold glucose con- centrations (≤6.5 mM). In cultured B-cells, GLP-1(7–36)amide produced a decrease of the whole-cell ATP-sensitive K+ (KATP) conductance remaining at 5 mM glucose by ≈30%. This effect was associated with membrane depolarization and the initiation of electrical activity. GLP-1(7–36)amide produced a protein-kinase-A- (PKA-) and glucose-dependent fourfold potentiation of Ca2+-induced exocytosis whilst only increasing the Ca2+ current marginally. The stimulatory action of GLP-1(7–36)amide on exocytosis was mimicked by the pancreatic hormone glucagon and exendin-4, a GLP-1 receptor agonist. Whereas the stimulatory action of GLP-1(7–36)amide could be antagonized by exendin-(9–39), this peptide did not interfere with the ability of glucagon to stimulate exocytosis. We suggest that GLP-1(7–36)amide and glucagon stimulate insulin secretion by binding to distinct receptors. The GLP-1(7–36)amide-induced stimulation of electrical activity and Ca2+ influx can account for (maximally) a doubling of insulin secretion. The remainder of its stimulatory action results from a cAMP/PKA-dependent potentiation of Ca2+-dependent exocytosis exerted at a stage distal to the elevation of [Ca2+]i.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050431
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  • 36
    Electronic Resource
    Electronic Resource
    The β cell transcription factors and development of the pancreas (1997)
    Springer
    Journal of molecular medicine 75 (1997), S. 327-340 
    Details
    ISSN: 1432-1440
    Keywords: Key words Pancreas ; Islet ; β Cell ; Insulin ; Transcription ; PDX-1 ; Development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The pancreatic β cell is the major source of circulating insulin in adult mammals. In the multistep process of insulin synthesis it is initiation of transcription that restricts insulin synthesis to the β cell since all subsequent steps can be performed by other cell types. Many of the transcription factors that bind to the insulin promoter and activate insulin gene transcription have been isolated. Some of these factors are restricted in their expression pattern, but so far no truly β cell-specific transcriptional activator has been found. Since different transcription factors synergize to activate insulin gene transcription, cell-specific transcription of insulin is probably realized through the interactions of a unique set of regulatory proteins in the β cell. The same transcription factors that regulate insulin gene transcription in the adult β cell are involved in determining cell differentiation during pancreatic development. The endocrine and exocrine pancreas form from the gut endoderm as a dorsal and a ventral bud which later fuse to build a single organ. The homeodomain protein PDX-1, an insulin gene transcription factor, is uniformly expressed in the early pancreatic bud, and null mutation of PDX-1 in mice results in a failure of the pancreatic bud to grow and differentiate. Other transcription factors, such as the helix-loop-helix protein Beta-2 and the homeodomain protein Nkx 6.1, show a restricted pattern of expression during embryogenesis and in the mature islet. Those proteins may serve a dual role for the organism: during embryogenesis they may determine islet cell differentiation and in the adult they may ensure tissue-specific expression of the islet cell hormones. A better understanding of the factors involved in insulin gene transcription and islet cell differentiation will ultimately provide the basis for novel therapy of diabetes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001090050118
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  • 37
    Electronic Resource
    Electronic Resource
    Effects of reduced electrochemical Na+ gradient on contractility in skeletal muscle: role of the Na+-K+ pump (1997)
    Springer
    Pflügers Archiv 434 (1997), S. 457-465 
    Details
    ISSN: 1432-2013
    Keywords: Key words Na+-K+ pump ; Membrane potential ; Muscle fatigue ; Catecholamines ; Insulin ; Soleus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Continued excitation of skeletal muscle may induce a combination of a low extracellular Na+ concentration ([Na+]o) and a high extracellular K+ concentration ([K+]o) in the T-tubular lumen, which may contribute to fatigue. Here, we examine the role of the Na+-K+ pump in the maintenance of contractility in isolated rat soleus muscles when the Na+, K+ gradients have been altered. When [Na+]o is lowered to 25 mM by substituting Na+ with choline, tetanic force is decreased to 30% of the control level after 60 min. Subsequent stimulation of the Na+-K+ pump with insulin or catecholamines induces a decrease in [Na+]i and hyperpolarization. This is associated with a force recovery to 80–90% of the control level which can be abolished by ouabain. This force recovery depends on hyperpolarization and is correlated to the decrease in [Na+]i (r = 0.93; P〈0.001). The inhibitory effect of a low [Na+]o on force development is considerably potentiated by increasing [K+]o. Again, stimulation of the Na+-K+ pump leads to rapid force recovery. The Na+-K+ pump has a large potential for rapid compensation of the excitation-induced rundown of Na+, K+ gradients and contributes, via its electrogenic effect, to the membrane potential. We conclude that these actions of the Na+-K+ pump are essential for the maintenance of excitability and contractile force.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050421
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  • 38
    Electronic Resource
    Electronic Resource
    Impacts of components of the metabolic syndrome on health status and survival in an aged population (1997)
    Springer
    European journal of epidemiology 13 (1997), S. 429-434 
    Details
    ISSN: 1573-7284
    Keywords: Elderly ; Health-status ; Insulin ; Lipids ; Metabolic-syndrome ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The clinical significances of different components of the multiple metabolic syndrome were studied in a five-year follow-up study of random persons (n = 1,199) of four birth cohorts at ages 65, 75, 80, and 85 years. The subjects were examined clinically and their serum lipids, blood glucose, plasma insulin, blood pressure, and health score were determined. The health score was measured using a visual analogue scale. All subjects were followed for 5 years. Health score, diastolic blood pressure and body mass index declined over age, but serum triglycerides, and blood glucose were similar, whilst serum high density lipoprotein (HDL)-cholesterol increased. Among women fasting plasma insulin was lowest in the age group of 65 years. The associations of components of the multiple metabolic syndrome varied by age. In the age groups of 65 and 75 years high body mass index, plasma insulin, glucose, triglycerides and low HDL-cholesterol were associated with impaired health. In the age group of 85 years high blood pressure, total cholesterol, and HDL-cholesterol were associated with good health. The baseline health score was consistently lower in the decedents than survivors of all age groups, but components of the metabolic syndrome were generally not associated with impaired survival.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007325609315
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  • 39
    Electronic Resource
    Electronic Resource
    Morphologische Wirkung von Adrenalin und Insulin auf Knochenkapillaren nach Rezeptorenblockade (1997)
    Springer
    Langenbeck's archives of surgery 382 (1997), S. 164-166 
    Details
    ISSN: 1435-2451
    Keywords: Key words Cortical bone ; Capillaries ; TEM ; Receptor blockade ; Epinephrine ; Insulin ; Schlüsselwörter Knochenkapillaren ; TEM ; Rezeptorenblockade ; Adrenalin ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 3mal sechs Mäusen wurden die α- und β-Rezeptoren mit Phentolamin und Propranolol blockiert. Den 3 Gruppen wurden Kochsalz, Adrenalin und Insulin injiziert. Kortikale Knochenkapillaren aus der Tibiadiaphyse wurden für die TEM aufgearbeitet. Ihre Lumen- und Endothelflächen wurden als Estimator angegeben und gruppenweise verglichen. Signifikante Änderungen wurden nur im Endothel nach Insulin gesehen. Das spricht für spezifische Insulinrezeptoren in der terminalen Strombahn von Knochen und bestätigt frühere Beobachtungen von Adrenalinwirkungen.
    Notes: Abstract In three groups of six mice each, the α- and β-receptors were blocked by phentolamine and propranolol. The mice in the three groups then received an intravenous bolus injection of saline solution, epinephrine, and insulin, respectively. Cortical bone capillaries from the tibia diaphysis were submitted to transmission electron microscopy (TEM). The lumen and endothelium were measured and the results compared. Significant changes were only noted in the endothelium after the administration of insulin. These findings suggest that there are also insulin receptors in bone. Furthermore, they support previous findings in similar studies with epinephrine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00008036
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  • 40
    Electronic Resource
    Electronic Resource
    Urinary phosphate excretion in the pathophysiology of idiopathic recurrent calcium urolithiasis: Hormonal interactions and lipid metabolism (1997)
    Springer
    Urological research 25 (1997), S. 417-426 
    Details
    ISSN: 1434-0879
    Keywords: Phosphaturia ; Glucose ; Insulin ; lipids ; Idiopathic recurrent calcium urolithiasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous work in younger males with recurrent idiopathic calcium urolithiasis (RCU) demonstrated inappropriately high postprandial phosphaturia, hyperinsulinemia and insulin resistance, but normal glycemia. To investigate further whether these abnormalities occur also in RCU patients with a mean age corresponding to the life period with peak formation of calcium-containing stones, two trials were carried out in 155 males of comparable age and body mass index. All participants underwent a standardized laboratory examination, including collection of urine and blood before and following a test meal rich in carbohydrate and calcium but low in phosphorus. In trial 1, comprising control subjects (n = 12, mean age 42 years) and RCU patients (n = 24, mean age 41 years), phosphate (Pi) excretion and fractional Pi excretion in postprandial urine of controls did not change compared with the values in fasting urine, but were significantly increased in RCU, despite the fact that there was almost equal suppression of serum parathyroid hormone (PTH) and increase in serum calcitonin. Postprandially, RCU patients were hyperinsulinemic but still normoglycemic versus controls. In trial 2, carried out in unclassified (in terms of calciuria) RCU patients (n = 119, mean age 40 years) only, the post-load Pi-uria was similar in magnitude to Pi-uria of RCU patients in trial l; increased postprandial Pi-uria was a phenomenon also of normocalciuria but was slightly more pronounced in hypercalciuria, while changes in calcium phosphate (brushite) and calcium oxalate supersaturation of urine were unrelated to calciuria. In RCU patients, but not controls, there was a tendency toward higher urinary glucose in post-load as compared with fasting urine. When urinary Pi and fractional Pi excretion in trial 2 were considered as dependent variables in multivariate regression analysis, they appeared unrelated to age, but positively associated with postprandial glycemia as the best predictor, followed by insulinemia, insulin resistance, to a lesser degree fasting serum PTH and the metabolic activity of stone disease, negatively associated with blood total lipids and very low density lipoprotein (VLDL) cholesterol. It was concluded that RCU males (1) show low Piuria during fasting but impaired renal Pi conservation in response to a mixed meal, a situation carrying the risk of Pi deficiency over the long term; (2) represent a population developing hyperei-uria despite suppressed PTH; (3) exhibit insulin resistance but are still able to maintain normoglycemia at the expense of hyperinsulinemia. It is suggested that calcium-containing renal stones are related to impaired Pi and glucose translocation across cell membranes, and that the role of lipids in this setting deserves further investigation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01268860
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  • 41
    Electronic Resource
    Electronic Resource
    Beta-endorphin infusion alters pancreatic hormone and glucose levels during exercise in rats (1997)
    Springer
    European journal of applied physiology 76 (1997), S. 203-208 
    Details
    ISSN: 1439-6327
    Keywords: Key words Naloxone ; Insulin ; Glucagon ; C-peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract β-Endorphin (BE) infusion at rest can influence insulin and glucagon levels and thus may affect glucose availability during exercise. To clarify the effect of BE on levels of insulin, glucagon and glucose during exercise, 72 untrained male Sprague-Dawley rats were infused i.v. with either: (1) BE (bolus 0.05 mg · kg−1 +0.05 mg · kg−1 · h−1, n = 24); (2) naloxone (N, bolus 0.8 mg · kg−1 + 0.4 mg · kg−1, n = 24); or (3) volume-matched saline (S, n = 24). Six rats from each group were killed after 0, 60, 90 or 120 min of running at 22 m · min−1, at 0% gradient. BE infusion resulted in higher plasma glucose levels at 60 min [5.93 (0.32) mM] and 90 min [4.16 (0.29) mM] of exercise compared to S [4.62 (0.27) and 3.41 (0.26 mM] and N [4.97 (0.38) and 3.44 (0.25) mM]. Insulin levels decreased to a greater extent with BE [21.5 (0.9) and 18.3 (0.6) uIU · ml−1] at 60 and 90 min compared to S [24.5 (0.5) and 20.6 (0.6) uIU · ml−1] and N [24.5 (0.4) and 21.6 (0.7) uIU · ml−1] groups. Plasma C-peptide declined to a greater extent at 60 and 90 min of exercise with BE infusion compared to both S and N. BE infusion increased glucagon at all times during exercise compared to S and N. These data suggest that BE infusion during exercise influences plasma glucose by augmenting glucagon levels and attenuating insulin release.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004210050237
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  • 42
    Electronic Resource
    Electronic Resource
    Metabolic and hormonal responses during repeated bouts of brief and intense exercise: effects of pre-exercise glucose ingestion (1997)
    Springer
    European journal of applied physiology 76 (1997), S. 197-202 
    Details
    ISSN: 1439-6327
    Keywords: Key words Glucose ; Insulin ; Epinephrine ; Lactate ; Force-velocity test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated metabolic and hormonal responses during repeated bouts of brief and intense exercise (a force-velocity test; Fv test) and examined the effect of glucose ingestion on these responses and on exercise performance. The test was performed twice by seven subjects [27 (2) years] according to a double-blind randomized crossover protocol. During the experimental trial (GLU), the subjects ingested 500 ml of glucose polymer solution containing 25 g glucose 15 min before starting the exercise. During the control trial (CON), the subjects received an equal volume of sweet placebo (aspartame). Exercise performance was assessed by calculating peak anaerobic power ( W˙ an,peak). Venous plasma lactate concentration increased significantly during the Fv test (P 〈 0.001), but no difference was found between CON and GLU. Blood glucose first decreased significantly from the beginning of exercise up to the 6-kg load (P 〈 0.001) and then increased significantly at W˙ an,peak and for up to 10 min during the recovery period (P 〈 0.001) in both CON and GLU. Insulin concentrations decreased significantly in both groups, but were higher at W˙ an,peak in GLU compared with CON (P 〈 0.05). Glucagon and epinephrine did not change significantly in either group, but epinephrine was significantly lower in GLU after glucose ingestion (P 〈 0.05) and at W˙ an,peak (P 〈 0.05). W˙ an,peak was not significantly different between CON and GLU. In conclusion, blood glucose and insulin concentrations decreased during repeated bouts of brief and intense exercise, while blood lactate concentration increased markedly without any significant change in glucagon and epinephrine concentrations. Glucose ingestion altered metabolic and hormonal responses during the Fv test, but the performance as measured by W˙ an,peak was not changed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004210050236
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  • 43
    Electronic Resource
    Electronic Resource
    The effect of zinc(II) and some chromium complexes on the constant current chronopotentiometry of insulin (1997)
    Weinheim : Wiley-Blackwell
    Electroanalysis 9 (1997), S. 554-559 
    Details
    ISSN: 1040-0397
    Keywords: Insulin ; Zinc ; Chromium ; Chronopotentiometry ; Disulfide ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The constant current chronopotentiometry (CCCP) of zinc-free insulin was examined and the effect of additions of zinc(II) or either of two chromium complexes to the zinc-free zinc was studied. The zinc free insulin gave a constant current chronopotentiometric (CCCP) response which indicated that the freeze drying process, which was part of its preparation, may have denatured the insulin. The addition of zinc(II) appeared to reverse this since the response following zinc additions was similar to that of native insulin. Of the two chromium complexes investigated for their influence on insulin electrochemistry tripicolinato chromium(III) had no effect on the CCCP response, trans-Diaquoethylenebis-(salicylideneiminato) chromium(III) had an indirect effect by appearing to restore the native conformation of the insulin following the apparent denaturation caused by the removal of zinc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/elan.1140090710
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  • 44
    Electronic Resource
    Electronic Resource
    Loss of GLUT2 glucose transporter expression in pancreatic beta cells from diabetic Chinese hamsters (1996)
    Springer
    Virchows Archiv 428 (1996), S. 177-185 
    Details
    ISSN: 1432-2307
    Keywords: Diabetic Chinese hamster ; Pancreatic beta cell ; Immunocytochemistry ; Insulin ; GLUT2 glucose transporter
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The diabetic Chinese hamster is a well-established animal model for NIDDM with a defective glucose-induced insulin secretory response. In the pancreas of nondiabetic hamsters, the GLUT2 glucose transporter was localized in the plasma membrane of insulin-positive beta cells. At variance with the rat, immunoreactivity was also detected in the cytoplasm. Other islet cell types were not GLUT2 positive. GLUT2 immunoreactivity was already significantly reduced in beta cells from mildly diabetic animals in spite of a normal insulin immunoreactivity. In severely diabetic animals the majority of the beta cells had lost GLUT2 immunostaining. This observation was confirmed in a Western blot analysis of the GLUT2 protein in isolated pancreatic islets. Only beta cells that were densely immunostained for insulin were still GLUT2 positive. However, around 40% of the beta cells devoid of GLUT2 immunoreactivity were still insulin immunoreactive. Thus, the loss of GLUT2 immunoreactivity, which is an important component of the glucose recognition apparatus of the pancreatic beta cell, is an early indicator of beta cell dysfunction before the development of degenerative lesions or the loss of insulin immunoreactivity. GLUT2 loss may be important in the deterioration of glucose-induced insulin secretion in the diabetic Chinese hamster.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00200660
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  • 45
    Electronic Resource
    Electronic Resource
    Insulin increases histomorphometric indices of bone formation In vivo (1996)
    Springer
    Calcified tissue international 59 (1996), S. 492-495 
    Details
    ISSN: 1432-0827
    Keywords: Insulin ; Osteoblasts ; In vivo ; Calvariae ; Histomorphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Recent clinical studies have established that bone density is related to both fat mass and circulating insulin levels. A direct action of insulin on the osteoblast may contribute to these relationships. Osteoblast-like cells have insulin receptors, and insulin has been shown to stimulate proliferation of these cells in vitro. However, it has not been possible to study the effects of insulin administration on bone in vivo because of the metabolic effects of insulin, particularly hypoglycemia. A model involving the local injection of insulin over one hemicalvaria of an adult mouse overcomes these difficulties and permits the histomorphometric study of insulin's action on bone. Insulin or vehicle was injected daily for 5 days over the right hemicalvariae of adult mice, and the animals were sacrificed 1 week later. All indices of bone formation were significantly increased in imsulin-treated hemicalvariae compared with the noninjected hemicalvariae. There was a 2.73±0.50-fold increase in osteoid area (P=0.0005), a 2.20±0.37-fold increase in osteoblast surface (P=0.021) and a 2.04±0.29-fold increase in osteoblast number (P=0.021). Indices of bone resorption tended to decline and mineralized bone area tended to increase in insulin-treated animals. The direct action of insulin on bone may contribute to the increased bone density seen in obesity and to the osteopenia of type I diabets, conditions associated with insulin excess and deficiency, respectively.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00369216
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  • 46
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    Electronic Resource
    Bombyxin gene expression in tissues other than brain detected by reverse transcriptionpolymerase chain reaction (RT-PCR) and in situ hybridization (1996)
    Springer
    Cellular and molecular life sciences 52 (1996), S. 882-887 
    Details
    ISSN: 1420-9071
    Keywords: Insulin ; insulin-like growth factor ; Bombyx mori ; ovary ; neurosecretory peptide ; Oligotex reverse transcription-polymerase chain reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Bombyxin is a 5 kDa insulin-related peptide produced in four pairs of medial neurosecretory cells in the brain of the silkmothBombyx mori. We demonstrate here the presence of bombyxin mRNA in tissues other than brain: ganglia, epidermis, testis, ovary, fat body, silk gland, Malpighian tubule, midgut, and hindgut of theBombyx fifth instar larvae. Bombyxin mRNA was detected by Oligotex reverse transcription-polymerase chain reaction (RT-PCR), a rapid and simple procedure of reverse transcription-PCR, and in situ hybridization. The Oligotex RT-PCR method effectively eliminated the contaminating DNA in RNA samples and amplified bombyxin mRNA efficiently. In situ hybridization of theBombyx ovary clearly demonstrated the localization of the bombyxin mRNA in the ovariole. The present study is the first demonstration of expression of brain neurosecretory peptide in tissues other than the central nervous system in insects at RNA level.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01938875
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  • 47
    Electronic Resource
    Electronic Resource
    Some thoughts on the importance of insulin in the regulation of the blood glucose level (1996)
    Springer
    Cellular and molecular life sciences 52 (1996), S. 421-425 
    Details
    ISSN: 1420-9071
    Keywords: Insulin ; fatty acids ; insulin-like growth factors ; Cori cycle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Insulin can influence rates of glucose utilization by muscle and possibly other tissues via both direct and indirect effects. It can control the rate of fatty acid mobilization from adipose tissue and the rate of fatty acid oxidation in muscle, and the latter inhibits glucose utilization and oxidation. Insulin may influence the levels of insulin-like growth factors I and II, both of which have effects on rates of glucose utilization by muscle. The intertissue cycle between glucose and lactate — the Cori cycle, which is influenced by insulin — may provide another novel mechanism for control of blood glucose. How far other anti-insulin hormones affect these processes is not clear.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01919310
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  • 48
    Electronic Resource
    Electronic Resource
    Investigations of receptor-mediated phagocytosis by hormone-induced (imprinted)Tetrahymena pyriformis (1996)
    Springer
    Cellular and molecular life sciences 52 (1996), S. 769-773 
    Details
    ISSN: 1420-9071
    Keywords: Insulin ; imprinting ; Tetrahymena ; phagocytosis ; insulin receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Receptor-mediated endocytosis byTetrahvmena pyriformis was studied using tetramethylrhodamine isothiocyanate-labeled concanavalin A (TRITC-Con A) with fluorescence and confocal microscopy. In the presence of insulin, or 24 h after insulin pretreatment (hormonal imprinting), the binding and uptake of TRITC-Con A increased when compared to controls, owing to the binding of TRITC-Con A to sugar oligomers of insulin recptors. Mannose inhibited the binding of Con A, thus demonstrating the specificity of binding. Histamine, a phagocytosis-promoting factor in mammals andTetrahymena, and galactose, did not influence the uptake of TRITC-Con A.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01923987
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  • 49
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    Electronic Resource
    Hyperinsulinemia, hyperproinsulinemia and insulin resistance in the metabolic syndrome (1996)
    Springer
    Cellular and molecular life sciences 52 (1996), S. 426-432 
    Details
    ISSN: 1420-9071
    Keywords: Insulin ; proinsulin ; insulin resistance ; metabolic syndrome ; triglycerides ; free fatty acids ; fat intake ; galanin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract For better comprehension of the metabolic syndrome, it is necessary to differentiate the effect of insulin on glucose metabolism on the one hand, and on other metabolic activities on the other hand. Whereas glucose utilization is affected by insulin resistance, the effect of insulin on lipid metabolism, ion and aminoacid transport does not seem to be diminished. Lipid metabolism, however, seems to play a crucial role in the induction of the vicious cycle. Increased energy and fat ingestion may be due to an increased number of galanin secreting cells in the hypothalamus. The excessive fat intake results in an increased rate of release of insulin and increased influx of triglycerides into the blood. From these triglycerides an excess of free fatty acids is released by the action of lipoprotein lipase. The increased plasma free fatty acid level then results in insulin resistance affecting glucose metabolism. Also, these free fatty acids may impair the secretion of insulin. Induction of insulin resistance results in higher glucose levels, which may cause hyperinsulinemia. Hyperinsulinemia maintains the elevation of triglycerides. When diabetes becomes overt and elevated glucose levels prevail, the hyperinsulinism acts on the metabolic pathways which are still sensitive to insulin, namely lipid metabolism, aminoacid transport and ion transport.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01919311
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  • 50
    Electronic Resource
    Electronic Resource
    An immunohistochemical analysis of the ontogeny, distribution and coexistence of 12 regulatory peptides and serotonin in endocrine cells and nerve fibers of the digestive tract of the turbot, Scophthalmus maximus (Teleostei) (1996)
    Springer
    Anatomy and embryology 195 (1996), S. 87-101 
    Details
    ISSN: 1432-0568
    Keywords: Key words Gastro-entero-endocrine cells ; Enteric nerve fibers ; Insulin ; Glucagon ; Somatostatin ; Pancreatic polypeptide ; Neuropeptide Y ; Insulin-like growth factor I ; Pancreastatin ; Neurotensin ; Substance P ; Gastrin ; Cholecystokinin ; Vasoactive intetinal polypeptide ; Serotonin ; Development ; Scophthalmus maximus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The ontogeny of endocrine cells and nerve fibers containing immunoreactivities for 12 regulatory peptides and serotonin was studied in the digestive tract of a flatfish, the turbot (Scophthalmus maximus), using antisera specific for mammalian and teleostean hormones. Transient insulin-immunoreactive (-IR) endocrine cells were detected from day 5 to day 10 in stomach and intestine I. Somatostatin (SOM)-IR cells appeared at day 8 in the stomach anlage and intestine I. In contrast to the islet cells, they reacted with antisera against mammalian (m) SOM-14 and salmon (s) SOM-25. Infrequent nerve fibers reacting only with anti-mSOM-14 appeared around day 24. Thus, different forms of SOM seem to be present in the gastro-entero-pancreatic system and the enteric nervous system. Neuropeptide Y (NPY)-, salmon pancreatic polypeptide (sPP)- and mPP-immunoreactivities coexisted thoughout development. In entero-endocrine cells, NPY/PP-immunoreactivity was first observed at day 8 and around day 24 in enteric nerve fibers. Glucagon (GLUC)-IR entero-endocrine cells appeared at day 5. No coexistence of NPY/PP- and GLUC-immunoreactivities was observed. The first insulin-like growth factor I (IGF-I)-IR cells were identified around day 8. They seemed to contain none of the other peptides. Their number and distribution exhibited great interindividual differences. Vasoactive intestinal polypeptide (VIP)-IR entero-endocrine cells appeared as late as around day 24. The first VIP-IR nerve fibers, however, were identified at day 5. Infrequent neurotensin (NT)-IR cells appeared along the intestine around day 10 and NT-IR nerve fibers at day 17. The first serotonin (SER)-IR cells were observed in the stomach anlage around day 10 and SER-IR nerve fibers at day 15 thoughout the gastro-intestinal tract. Gastrin (GAS)/cholecystokinin (CCK)-IR cells appeared around day 11 in stomach and intestine I. The first substance P (SP)-IR enteric nerve fibers were detected around day 8 and SP-IR endocrine cells at day 11. Pancreastatin (PST)-IR cells were identified in the stomach anlage and intestine I around day 8 and contained NT-, GAS/CCK- and SER-immunoreactivities in coexistence. Thus, several developmental phases can be distinguished: (1) at the onset of exogenous feeding only transient INS-IR cells and VIP-IR nerve fibers are present; (2) a differentiated entero-endocrine system establishes during the early phase of exogenous feeding; (3) before the final differentiation of stomach and gut GAS/CCK-IR cells appear; (4) after metamorphosis most of the different types of regulatory peptide-containing nerve fibers develop, probably setting up the fine regulation of gastro-intestinal blood flow and motility.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004290050028
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  • 51
    Electronic Resource
    Electronic Resource
    Endothelin-1 and insulin induce cellular inactivation of protein kinase FA/glycogen synthase kinase-3α in a common signaling pathway (1996)
    Springer
    Journal of biomedical science 3 (1996), S. 275-279 
    Details
    ISSN: 1423-0127
    Keywords: Endothelin-1 ; Insulin ; Protein Kinase FA/GSK-3α ; MAP kinase signaling pathway ; Rat adipocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract In this study, we investigate the effects of endothelin-1 (ET-1) and insulin on the cellular activity of protein kinase FA/glycogen synthase kinase-3α (kinase FA/GSK-3α) in rat adipocytes. The cellular activity of kinase FA/GSK-3α is inhibited to ∼ 50% of control within 30 min when cells are treated with 1 nM ET-1 at 37°C; in addition, significant inhibition to ∼ 60% of control is observed at as low as 1 pM ET-1. Conversely, ET-1 at concentrations up to 1 nM has no direct effect on purified kinase FA/GSK-3α in vitro. Immunoblotting analysis further reveals that the protein level of this kinase is not significantly changed when treated with 1 nM ET-1 for 30 min. Similar to ET-1, insulin as low as 10 nM can also induce inactivation of kinase FA/GSK-3α to ∼ 50% of control in adipocytes when processed under identical conditions. Most importantly, when treated with both insulin and ET-1, the activity of kinase FA/GSK-3α can be decreased only to ∼ 50% of control. Taken together, the results provide initial evidence that ET-1 and insulin may regulate this important multisubstrate/multifunctional protein kinase in a common signaling pathway in cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02253707
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  • 52
    Electronic Resource
    Electronic Resource
    GTPase activating protein activity for Rab4 is enriched in the plasma membrane of 3T3-L1 adipocytes. Possible involvement in the regulation of Rab4 subcellular localization (1996)
    Springer
    Diabetologia 39 (1996), S. 899-906 
    Details
    ISSN: 1432-0428
    Keywords: Insulin ; small GTPases ; GLUT4 ; translocation ; adipocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The small guanosine 5′-triphosphate (GTP)ase Rab4 has been suggested to play a role in insulin-induced GLUT4 translocation. Under insulin stimulation, GLUT4 translocates to the plasma membranes, while Rab4 leaves the GLUT4-containing vesicles and becomes cytosolic. Rab proteins cycle between a GTP-bound active form and a guanosine 5′-diphosphate (GDP)-bound inactive form. The intrinsic GTPase activity of Rab proteins is low and the interconversion between the two forms is dependent on accessory factors. In the present work, we searched for a GTPase activating protein (GAP) for Rab4 in 3T3-L1 adipocytes. We used a glutathione-S-transferase (GST)-Rab4 protein which possesses the properties of a small GTPase (ability to bind GDP and GTP and to hydrolyse GTP) and can be isolated in a rapid and efficient way. This GAP activity was observed in 3T3-L1 adipocyte lysates, and was able to accelerate the hydrolysis of the [α-32P]GTP bound to GST-Rab4 into [α-32P]GDP. This activity, tentatively called Rab4-GAP, was also present in 3T3-L1 fibroblasts. The Rab4-GAP activity was present in total membrane fractions and nearly undetectable in cytosol. Following subcellular fractionation, Rab4-GAP was found to be enriched in plasma membranes when compared to internal microsomes. Insulin treatment of the cells had no effect on the total Rab4-GAP activity or on its subcellular localization. Taking our results together with the accepted model of Rab cycling in intracellular traffic, we propose that Rab4-GAP activity plays a role in the cycling between the GTP- and GDP-bound forms of Rab4, and thus possibly in the traffic of GLUT4-containing vesicles.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403908
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  • 53
    Electronic Resource
    Electronic Resource
    Insulin-induced activation of phosphoinositide 3-kinase in Fao cells (1996)
    Springer
    Diabetologia 39 (1996), S. 515-522 
    Details
    ISSN: 1432-0428
    Keywords: Insulin ; insulin receptor substrate-1 ; phosphoinositide 3-kinase ; signal transduction ; phosphotyrosine ; enzyme activation ; conformational change ; Fao cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Phosphoinositide 3-kinase (PI3-kinase) plays a crucial role in insulin signal transduction. We studied the molecular mechanism of the insulin-induced activation of PI3-kinase in rat hepatoma Fao cells using an antibody against the 110-kDa catalytic subunit (p110) and two against the 85-kDa regulatory subunit (p85α). PI3-kinase activity increased 1.6-fold in anti-p85 immunoprecipitates after insulin stimulation, whereas it did not increase when cell lysates were first immunoprecipitated with anti-phosphotyrosine or anti-insulin receptor substrate-1 (IRS-1), then with anti-p85, suggesting that the PI3-kinase which associates with tyrosyl phosphoproteins including IRS-1 is responsible for the increase in kinase activity. The activated PI3-kinase molecules constituted 4–6% of the total PI3-kinase, and their specific activity was 11–14 times higher than that of the basal state. Anti-p110 recognized the catalytically active form of p110, and immunoprecipitated p110 only after exposure to insulin. Hence, the epitope of anti-p110, P200-C215, seems to be included in the portion of p110, the conformation of which is changed by insulin stimulation. We conclude that, in response to insulin stimulation, only a small fraction of p85 in the PI3-kinase pool associates with tyrosyl phosphoproteins including IRS-1, and that the specific activity of p110 is increased presumably through a conformational change including the P200-C215 region.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403297
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  • 54
    Electronic Resource
    Electronic Resource
    Response to insulin and the expression pattern of a gene encoding an insulin receptor homologue suggest a role for an insulin-like molecule in regulating growth and patterning in Hydra (1996)
    Springer
    Development genes and evolution 206 (1996), S. 247-259 
    Details
    ISSN: 1432-041X
    Keywords: Key words Hydra ; Insulin ; Development ; Receptor ; Evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  A gene encoding a receptor protein-tyrosine kinase closely related to the vertebrate insulin receptor has been identified in the Cnidarian Hydra vulgaris. The gene is expressed in both epithelial layers of the adult polyp. A particularly high level of expression is seen in the ectoderm of the proximal portions of the tentacles and in a ring of ectodermal cells at the border between the foot basal disk and body column. The expression pattern of the gene in asexual buds is dynamic; expression is high throughout the newly emerging bud but the area of high expression becomes restricted to the apex as the bud lengthens. When the bud begins hypostome and tentacle formation, a high level of expression appears at the bases of the emerging tentacles. Finally, a ring of high expression appears just above the foot of the bud, completing the pattern seen in the adult polyp. The presence of this receptor and its pattern of expression suggested that an endogenous molecule related to insulin plays a role in regulating cell division in the body column and in differentiation of the tentacle and foot cells in Hydra, with the switch between the two being determined by the level of the receptor. Treatment of Hydra polyps with mammalian insulin caused an increase in the number of ectodermal and endodermal cells undergoing DNA synthesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004270050050
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  • 55
    Electronic Resource
    Electronic Resource
    Energetics of cyclodextrin-induced dissociation of insulin (1996)
    Springer
    European biophysics journal 24 (1996), S. 354-357 
    Details
    ISSN: 1432-1017
    Keywords: Cyclodextrin ; Insulin ; Dimer Dissociation ; Microcalorimetry ; Thermodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract The energetics of dissociation of bovine insulin in aqueous solution have been investigated by sensitive dilution microcalorimetry. Cyclodextrins increase dissociation of insulin oligomers in a manner consistent with their interaction with protein side chains. For example, assuming monomer-dimer equilibrium, in the absence of cyclo-dextrins the calorimetric dilution data (25 °C, pH 2.5) indicate a dimer dissociation constant (Kdiss) of about 12 µM and an endothermic dissociation enthalpy (ΔHdiss) of +41 kJ mol−1. Addition of methyl-β-cyclodextrin (up to 200 mm) makes dissociation significantly more endothermic (ΔHdiss = 79 kJ mol−1) and reduces the apparent dimer dissociation constant by more than two orders of magnitude (Kdiss ≈ 1.7 mm). Qualitatively similar results are observed with α-cyclodextrin and other β-cyclodextrin derivatives. Cyclodextrin-induced insulin dissociation is also observed at pH 7.4.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00180377
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  • 56
    Electronic Resource
    Electronic Resource
    Neonatal diabetes and intra-uterine growth retardation (1996)
    Springer
    European journal of pediatrics 156 (1996), S. 1-2 
    Details
    ISSN: 1432-1076
    Keywords: Key words Neonatal diabetes mellitus ; Intra-uterine dystrophy ; Insulin ; Insulin-like growth factor␣I ; Fetal growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310050540
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  • 57
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    Electronic Resource
    Infusion of pH 2.0 d-chiro-inositol glycan insulin putative mediator normalizes plasma glucose in streptozotocin diabetic rats at a dose equivalent to insulin without inducing hypoglycaemia (1996)
    Springer
    Diabetologia 39 (1996), S. 731-734 
    Details
    ISSN: 1432-0428
    Keywords: Insulin ; mediator ; d-chiro-inositol ; euglycaemia ; manganese
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We compared the effects of infusing a chemically defined chiro-inositol glycan putative insulin mediator with an equivalent dose of insulin in low-dose (45 mg/kg) streptozotocin diabetic rats. Insulin decreased plasma glucose levels from 17.32±0.17 to 3.96±0.064 mmol/l (p〈0.0002) in 120 min, a decrease of 77.13%, while the putative mediator promoted a decrease in plasma glucose from 14.85±0.084 to 7.22±0.13 mmol/l (p〈0.007) in 60 min. The putative mediator maintained euglycaemia over the ensuing 60 min with a plasma glucose level of 7.01±0.10 mmol/l at 120 min. Thus, insulin further reduced the plasma glucose from euglycaemia at 60 min to produce hypoglycaemia at 120 min. The lack of production of hypoglycaemia by the putative mediator can be explained by its inhibition of glucose-stimulated insulin secretion by the islet beta cells, thus providing a potential negative feedback regulatory mechanism; or by its selective action on muscle to increase glycogen synthesis. The significance of these results in terms of future directions in drug design is herein considered.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00418546
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  • 58
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    Amiloride-blockable Ca2+-activated Na+-permeant channels in the fetal distal lung epithelium (1996)
    Springer
    Pflügers Archiv 431 (1996), S. 748-756 
    Details
    ISSN: 1432-2013
    Keywords: Benzamil ; Insulin ; Nonselective cation channel ; Na+ channel ; Alveolar cells ; Type II ; Single-channel recording
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The Na+ transport function of alveolar epithelium represents an important mechanism for clearance of fluid in air space at birth. I observed the activity of two types of amiloride-blockable Na+-permeant cation channels in the apical membrane of fetal distal lung epithelium cultured on permeable filters for 2 days after harvesting of the cells from Wistar rats of 20 days' gestation (term = 22 days). One type was a nonselective cation (NSC) channel and had a linear current/voltage (I/V) relationship with a single-channel conductance of 26.9 ± 0.8 pS (n = 5). The other type was highly Na+ selective (i.e. Na+ channel) and had an inwardly rectifyingI/V relationship with a single-channel conductance of 11.8 ± 0.2 pS (n = 5) around resting membrane potential. The NSC channel was more frequently observed (1.37 ± 0.15 per patch membrane;n = 73) than the Na+ channel (0.15 ± 0.40 per patch membrane;n = 73). However, the open probability of the NSC channel was smaller than that of the Na+ channel. Both types of the channels were activated by cytosolic Ca2+, however the sensitivity to cytosolic Ca2+ was much higher in the Na+ channel than in the NSC channel. Furthermore, both types of the channels were blocked by amiloride or benzamil. The half-maximal inhibitory concentration (IC50) of amiloride or benzamil of the Na+ channel was 1–2 μM, while that of NSC channel was less than 1 μM. Both channels were activated by insulin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02253839
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  • 59
    Electronic Resource
    Electronic Resource
    Amiloride-blockable Ca2+-activated Na+-permeant channels in the fetal distal lung epithelium (1996)
    Springer
    Pflügers Archiv 431 (1996), S. 748-756 
    Details
    ISSN: 1432-2013
    Keywords: Key words Benzamil ; Insulin ; Nonselective cation channel ; Na+ channel ; Alveolar cells ; Type II ; Single-channel recording
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The Na+ transport function of alveolar epithelium represents an important mechanism for clearance of fluid in air space at birth. I observed the activity of two types of amiloride-blockable Na+-permeant cation channels in the apical membrane of fetal distal lung epithelium cultured on permeable filters for 2 days after harvesting of the cells from Wistar rats of 20 days’ gestation (term = 22 days). One type was a nonselective cation (NSC) channel and had a linear current/voltage (I/V) relationship with a single-channel conductance of 26.9 ± 0.8 pS (n = 5). The other type was highly Na+ selective (i.e. Na+ channel) and had an inwardly rectifying I/V relationship with a single-channel conductance of 11.8 ± 0.2 pS (n = 5) around resting membrane potential. The NSC channel was more frequently observed (1.37 ± 0.15 per patch membrane; n = 73) than the Na+ channel (0.15 ± 0.40 per patch membrane; n = 73). However, the open probability of the NSC channel was smaller than that of the Na+ channel. Both types of the channels were activated by cytosolic Ca2+, however the sensitivity to cytosolic Ca2+ was much higher in the Na+ channel than in the NSC channel. Furthermore, both types of the channels were blocked by amiloride or benzamil. The half-maximal inhibitory concentration (IC50) of amiloride or benzamil of the Na+ channel was 1–2 μM, while that of NSC channel was less than 1 μM. Both channels were activated by insulin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050061
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  • 60
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    Effects of propionyl-L-carnitine and insulin on the electroretinogram, nerve conduction and nerve blood flow in rats with streptozotocin-induced diabetes (1996)
    Springer
    Pflügers Archiv 431 (1996), S. 564-570 
    Details
    ISSN: 1432-2013
    Keywords: Key words Propionyl-L-carnitine ; Insulin ; Streptozotocin-induced diabetic rat ; Motor nerve conduction velocity ; Sciatic nerve blood flow ; Electroretinogram ; Sorbitol ; myo-Inositol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of an analogue of L-carnitine, propionyl-L-carnitine, on the electroretinogram, motor nerve conduction velocity and nerve blood flow was determined in rats with streptozotocin-induced diabetes, and was compared with the effects of insulin alone or combined therapy. Oral administration of propionyl-L-carnitine (3 g/kg daily for 4 weeks) significantly increased caudal nerve motor conduction velocity and sciatic nerve blood flow in diabetic rats. There were no differences in the effects of insulin (8–10 U daily for 4 weeks), propionyl-L-carnitine and combined therapy. Although propionyl-L-carnitine significantly shortened the peak latency of the electroretinogram b-wave in diabetic rats, its effect was far weaker than that of insulin or combined therapy, with combined therapy producing the greatest improvement. These effects of propionyl-L-carnitine were accompanied by a decrease of serum lipid levels, an increase of the sciatic nerve carnitine content, and no changes of the tissue (nerve and retinal) sorbitol and myo-inositol concentrations. In contrast, insulin significantly reduced the tissue sorbitol content and markedly increased myo-inositol. These findings suggest that propionyl-L-carnitine may improve diabetic neuropathy and retinopathy without influencing the polyol pathway, and that this beneficial effect may be mediated through the amelioration of microcirculation and tissue carnitine content, thus probably increasing fatty acid oxidation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050036
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  • 61
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    Electronic Resource
    Effects of propionyl-l-carnitine and insulin on the electroretinogram, nerve conduction and nerve blood flow in rats with streptozotocin-induced diabetes (1996)
    Springer
    Pflügers Archiv 431 (1996), S. 564-570 
    Details
    ISSN: 1432-2013
    Keywords: Propionyl-l-carnitine ; Insulin ; Streptozotocin-induced diabetic rat ; Motor nerve ; conduction velocity ; Sciatic nerve blood flow ; Electroretinogram ; Sorbitol ; myo-Inositol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of an analogue ofl-carnitine, propionyl-l-carnitine, on the electroretinogram, motor nerve conduction velocity and nerve blood flow was determined in rats with streptozotocin-induced diabetes, and was compared with the effects of insulin alone or combined therapy. Oral administration of propionyl-l-carnitine (3 g/kg daily for 4 weeks) significantly increased caudal nerve motor conduction velocity and sciatic nerve blood flow in diabetic rats. There were no differences in the effects of insulin (8–10 U daily for 4 weeks), propionyl-l-carnitine and combined therapy. Although propionyl-l-carnitine significantly shortened the peak latency of the electroretinogram b-wave in diabetic rats, its effect was far weaker than that of insulin or combined therapy, with combined therapy producing the greatest improvement. These effects of propionyl-l-carnitine were accompanied by a decrease of serum lipid levels, an increase of the sciatic nerve carnitine content, and no changes of the tissue (nerve and retinal) sorbitol andmyo-inositol concentrations. In contrast, insulin significantly reduced the tissue sorbitol content and markedly increasedmyo-inositol. These findings suggest that propionyl-l-carnitine may improve diabetic neuropathy and retinopathy without influencing the polyol pathway, and that this beneficial effect may be mediated through the amelioration of microcirculation and tissue carnitine content, thus probably increasing fatty acid oxidation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02191904
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    Electronic Resource
    Characterization of hormone-stimulated Na+ transport in a high-resistance clone of the MDCK cell line (1996)
    Springer
    Pflügers Archiv 432 (1996), S. 685-691 
    Details
    ISSN: 1432-2013
    Keywords: Key words Aldosterone ; Insulin ; IGF1 ; ADH ; Vasopressin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The Madin-Darby canine kidney (MDCK) cell line forms an epithelial monolayer which expresses many of the morphological and functional properties of the renal collecting duct. The C7 subclone of the parent line forms an epithelium which expresses many of the characteristics of principal cells. The MDCK-C7 subclone forms a high-resistance epithelium that is capable of vectorial ion transport. We have found that this epithelium responds to aldosterone, antidiuretic hormone (ADH) and insulin like growth factor 1 (IGF1) with increases in amiloride-sensitive Na+ transport. The responses to aldosterone and ADH follow time-courses that are consistent with the action of these hormones in vivo. This is the first demonstration of IGF1-induced Na+ reabsorption in a mammalian model system. Interestingly, a maximal response to any one of these natriferic factors does not inhibit a subsequent response to another hormone. These studies indicate that the C7 subclone retains many of the natriferic responses of the native principal cells and is an ideal model for studying hormonal modulation of Na+ transport.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050186
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  • 63
    Electronic Resource
    Electronic Resource
    Derivative chronopotentiometric stripping analysis of insulin (1996)
    Weinheim : Wiley-Blackwell
    Electroanalysis 8 (1996), S. 49-54 
    Details
    ISSN: 1040-0397
    Keywords: Insulin ; Potentiometric stripping analysis ; Constant current stripping analysis ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Porcine insulin was analyzed in the presence of dissolved oxygen by constant current stripping analysis (CCSA) and potentiometric stripping analysis (PSA). The CCSA analysis involves the constant current reduction of mercuric insulin thiolate following its potentiostatic accumulation on a hanging mercury drop electrode. The CCSA response was quantitatively enhanced in the presence of dissolved oxygen. The PSA analysis involves the oxidation, by dissolved oxygen, of sulfhydryl groups in reduced insulin following its accumulation on the HMDE at -900mV (vs. SCE).
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/elan.1140080111
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  • 64
    Electronic Resource
    Electronic Resource
    Trace measurements of insulin by potentiometric stripping analysis at carbon paste electrodes (1996)
    Weinheim : Wiley-Blackwell
    Electroanalysis 8 (1996), S. 902-906 
    Details
    ISSN: 1040-0397
    Keywords: Insulin ; Myoglobin ; Protein ; Potentiometric stripping analysis ; Carbon paste electrode ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A potentiometric stripping method for trace measurements of insulin at carbon paste electrodes is described. The method is based on the controlled adsorptive accumulation of this polypeptide hormone at the anodically pretreated carbon surface followed by constant-current chronopotentiometric measurements of the surface species. A well-defined peak, associated with the oxidation of the tyrosine residues, is observed over the flat baseline of the potentiometric stripping operation. Variables of the pretreatment and measurement steps are optimized to offer a detection limit of 2 × 10-9M after 5 min preconcentration. Excess of nunierous potential interferences does not influence the response observed after transferring the electrode (with the accumulated insulin) to a blank electrolyte solution. A similar protocol is described for trace measurements of the protein myoglobin.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/elan.1140081010
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  • 65
    Electronic Resource
    Electronic Resource
    A novel mechanism of glipizide sulfonylurea action: decreased metabolic clearance rate of insulin (1995)
    Springer
    Acta diabetologica 32 (1995), S. 273-278 
    Details
    ISSN: 1432-5233
    Keywords: Sulfonylurea ; Glipizide ; C-peptide ; Insulin ; Insulin metabolic clearance rate (MCR1)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To examine whether sulfonylureas inhibit the metabolic clearance rate (MCR) of insulin, 19 healthy young subjects participated in two experiments. In the first protocol (n=10), a 3-h oral glucose load was performed with and without 2 mg of glipizide given 30 min before glucose ingestion. The total insulin response was 60% greater with than without glipizide (5.9±0.6 vs 3.7±0.5 μU/ml;P〈0.001). However, the total C-peptide responses were virtually identical (4.7±0.5 vs 4.8±0.4 nmol/l) in both studies. In the second protocol (n=9), the MCR of insulin was measured during 4-h euglycemic insulin clamps performed with and without glipizide. In the study with glipizide, the subjects ingested 5 mg of glipizide at 120 min. The steady-state plasma insulin concentration during the 4th h, i.e., 1–2 h after glipizide ingestion, was significantly higher than during the 2nd h, i.e., before glipizide ingestion (99±22 vs 78±17 μU/ml;P〈0.01). In addition, glucose uptake during the 4th h was greater (8.0±1.6 vs 6.4±1.5 mg/kg·min) and the MCR of insulin was reduced (503±126 vs 621±176 ml/m2·min;P〈0.01). We conclude that glipizide augments plasma insulin levels both by enhancing its secretion and by decreasing the MCR of insulin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00576262
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  • 66
    Electronic Resource
    Electronic Resource
    Interaction of glucagon-like peptide-I (GLP-I) and galanin in insulin (βTC-1)- and somatostatin (RIN T3)-secreting cells and evidence that both peptides have no receptors on glucagon (INR1G9)-secreting cells (1995)
    Springer
    Acta diabetologica 32 (1995), S. 176-181 
    Details
    ISSN: 1432-5233
    Keywords: Insulin ; Glucagon ; Somatostatin ; Glucagon-like peptide-I ; Galanin ; Incretin ; Decretin ; Adenylate cyclase ; Cyclic adenosine monophosphate ; Protein kinase A
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The interaction of glucagon-like peptide-I (GLP-I) and galanin in clonal endocrine pancreatic cells was characterized. By Northern blot analysis the presence of GLP-I receptor mRNA was shown in B (\TC-1 cells) and D (RIN 1048-38) cells but not in A (INR1 G9) cells, thus confirming functional data demonstrating the absence of active GLP-I receptors on glucagon-producing cells. Galanin receptors were detected on B and D cells but not on A cells. In B and D cells galanin inhibited the GLP-I stimulated adenylate cyclase activity. Treatment of insulin-and somatostatin-producing cells with GLP-I increased intracellular cAMP levels, and this was dampened by galanin. GLP-I stimulated the activity of protein kinase A in B and D cells, which was also inhibited by galanin. Galanin alone did not influence B- and D-cell function. These data show that in the endocrine pancreas B and D cells but not A cells express GLP-I and galanin receptors. The interaction of GLP-I and galanin occurs at the level of adenylate cyclase. Galanin might act in the endocrine pancreas as a physiological inhibitor of the potent incretin hormone GLP-I. Therefore, we suggest galanin is a ‘decretin’.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00838488
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  • 67
    Electronic Resource
    Electronic Resource
    Magnitude and modulation of pancreatic β-cell gap junction electrical conductance in situ (1995)
    Springer
    The journal of membrane biology 146 (1995), S. 163-176 
    Details
    ISSN: 1432-1424
    Keywords: Pancreatic islet ; Cell-to-cell coupling ; Calcium ; Burst ; Synchrony ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The parallel gap junction electrical conductance between a β-cell and its nearest neighbors was measured by using an intracellular microelectrode to clamp the voltage of a β-cell within a bursting islet of Langerhans. The holding current records consisted of bursts of inward current due to the synchronized oscillations in membrane potential of the surrounding cells. The membrane potential record of the impaled cell, obtained in current clamp mode, was used to estimate the behavior of the surrounding cells during voltage clamp, and the coupling conductance was calculated by dividing the magnitude of the current bursts by that of the voltage bursts. The histogram of coupling conductance magnitude from 26 cells was bimodal with peaks at 2.5 and 3.5 nS, indicating heterogeneity in extent of electrical communication within the islet of Langerhans. Gap junction conductance reversibly decreased when the temperature was lowered from 37 to 30°C and when the extracellular calcium concentration was raised from 2.56 to 7.56 mm. The coupling conductance decreased slightly during the active phase of the burst. Activation of adenylate cyclase with forskolin (10 μm) resulted in an increase in cell-to-cell electrical coupling. We conclude that β-cell gap junction conductance can be measured in situ under near physiological conditions. Furthermore, the magnitude and physiological regulation of β-cell gap junction conductance suggest that intercellular electrical communication plays an important role in the function of the endocrine pancreas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00238006
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  • 68
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    Electronic Resource
    Number and ultrastructure of epithelial cells in crypts and villi along the streptozotocin-diabetic small intestine: a quantitative study on the effects of insulin and aldose reductase inhibition (1995)
    Springer
    Virchows Archiv 427 (1995), S. 187-193 
    Details
    ISSN: 1432-2307
    Keywords: Diabetes ; Insulin ; Aldose reductase inhibition ; Small intestine ; Epithelial cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study has quantified the effects of insulin treatment with and without aldose reductase inhibitor (ponalrestat) on intestinal epithelial cell morphology in streptozotocin-diabetic rats. Epithelial volumes, villous and microvillous surface areas and mean volumes of cells (and their nuclei) in crypts and villi were estimated in each of four segments and in the entire intestine. We derived total numbers of cells, quantified the ultrastructural features of average cells and explored variation along the intestine and between experimental groups. In crypts, insulin and ponalrestat had significant effects on cell number (reduced towards normal values) and size (volume and apex area increased beyond normal values). There were interaction effects between insulin and ponalrestat for cell volume and apex area (insulin producing more exaggerated effects when given without ponalrestat). On villi, insulin and ponalrestat returned cell numbers towards normal values but neither treatment normalised cell size or the number and area of microvilli per cell. Indeed, ponalrestat increased microvillous number and area beyond values found in untreated diabetic animals. Again, there were interaction effects between insulin and ponalrestat. Patterns of segmental variation seen in crypts of normal rats (values tending to be higher in proximal or mid-intestinal regions) were not preserved, and only some of the segmental differences seen on villi (higher values at proximal or mid-intestinal sites) were maintained during therapy. Apart from reducing the abnormally high numbers of cells in untreated diabetic rats, these results show that insulin and ponalrestat treatment fail to restitute epithelial cell morphology in the small intestines of experimental diabetic rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00196525
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  • 69
    Electronic Resource
    Electronic Resource
    Parathyroid hormone decreases in vivo insulin effect on glucose utilization (1995)
    Springer
    Calcified tissue international 57 (1995), S. 127-132 
    Details
    ISSN: 1432-0827
    Keywords: Parathyroid hormone ; Insulin ; Glucose metabolism ; Calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract Hyperparathyroidism is associated with impaired glucose tolerance, and parathyroidectomy may improve carbohydrate homeostasis. It has been suggested that parathyroid hormone (PTH) suppresses insulin secretion but it is unclear whether it also interferes with the peripheral action of insulin. To evaluate in vivo effects of PTH on insulinmediated glucose utilization, 15 male Sprague Dawley rats were continuously infused with rat PTH (1–34) using an Alzet miniosmotic pump at a rate of 0.03 nm/hour. Controls were infused with the vehicle alone. Following 5 days of PTH infusion, plasma calcium (Ca) levels were higher in the PTH-infused rats (12.3±0.2 versus 9.9±0.1 mg/dl, P〈0.01). On the 5th day, glucose (700 mg/kg) and insulin (0.175 U/kg) were given as a bolus infusion through the left femoral vein, blood samples were obtained from the right femoral vein, and plasma glucose and insulin were measured at basal (0 minutes) and at 2, 5, 10, and 20 minutes postinfusion. Basal, nonfasting glucose levels were higher (166±4 versus 155±4 mg/dL, P〈0.04) in the PTH-infused rats but their insulin levels were similar to those of controls (6.5±0.6 versus 5.6 ±0.5 ng/ml). Postinfusions and maximal (2 minutes) glucose and insulin levels were similar in both groups. However, although insulin levels were similar in both groups at all measured time points, glucose levels at 20 minutes were higher in the PTH-treated rats (205±13 versus 173±9; P〈0.03). Also, calculated glucose disappearance rates (Kg) were decreased in the PTH-infused rats (4.05±0.3 versus 4.63±0.8; P=0.054), suggesting an impaired peripheral effect of insulin on glucose utilization. To gain insight into the potential contribution of the hypercalcemia or the PTH to these abnormalities, correlation evaluations were performed. Only in PTH-infused rats did plasma Ca correlate with plasma glucose at 0 and 20 minutes (r=0.6, P=0.02; r=0.7, P=0.01) and with the area under the glucose curve (r=0.6, P=0.03) during the glucose-insulin infusion. Also only in PTH-infused rats did PTH correlate with 0 (P=0.07) and 20-minute (P=0.02) plasma glucose levels. There was no correlation between either Ca or PTH and basal insulin levels or the area under the insulin curve in either group. Consequently, we suggest that in the rat, PTH infusion associated with hypercalcemia impairs insulin effect on glucose utilization in vivo and this defect may be induced by the Ca, PTH, or both.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00298433
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  • 70
    Electronic Resource
    Electronic Resource
    The effect of insulin on the vascular reactivity of isolated resistance arteries taken from healthy volunteers (1995)
    Springer
    Diabetologia 38 (1995), S. 467-473 
    Details
    ISSN: 1432-0428
    Keywords: Insulin ; resistance arteries ; vascular reactivity ; EDRF
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Impaired reactivity of the resistance vasculature may contribute to the development of diabetic microangiopathy by altering microvascular haemodynamics. This study investigates the acute effects of insulin on the contractility and relaxation properties of isolated human resistance arteries (〈300 Μm internal diameter) taken from gluteal subcutaneous fat of 33 (18 male: 15 female) normotensive healthy volunteers (supine blood pressure 115.6±1.6/ 70.0±1.5 mm Hg [mean±SEM], with no family history of hypertension or diabetes mellitus. Resistance arteries were mounted in a small vessel myograph to measure isometric tension. Contractile responses to noradrenaline were reduced after incubation in 1 mU/ml of insulin for 20 min (p〈0.01; Group 1). Increasing concentrations of insulin were found to reduce the contractile response to noradrenaline in a dose-dependent manner (Group 2; 0.1 mU/ml by 8% [p〈0.01], 1 mU/ml by 17% [p〈0.02] and 10 mU/ml by 22% [p〈 0.01]). Sensitivity to insulin (ED50) only decreased at the highest concentration of insulin. However, acetycholine-induced relaxation was not altered by insulin (Group 2). Time control studies (Group 3) showed that contractile and relaxation responses over the 4-h study period were unchanged. Furthermore, the length of time the vessels were exposed to insulin did not progressively impair responses (Group 4). These findings suggest that insulin may induce abnormalities in vascular smooth muscle contractility, a factor that may contribute to or exacerbate the abnormal haemodynamics observed in the capillary microcirculation of numerous vascular beds in diabetes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00410285
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  • 71
    Electronic Resource
    Electronic Resource
    In situ binding of islet hormones in the isolated perfused rat pancreas: evidence for local high concentrations of islet hormones via the islet-acinar axis (1995)
    Springer
    Diabetologia 38 (1995), S. 262-268 
    Details
    ISSN: 1432-0428
    Keywords: Insulin ; somatostatin ; glucagon ; islet-acinar portal system ; exocrine pancreas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin and somatostatin reportedly affect pancreatic acinar cell function via specific receptor binding. Theoretically peri-insular levels depend on the islet-acinar portal system, but the actual hormone levels have never been demonstrated. Rat pancreata were perfused anterogradely or retrogradely with 125I-insulin, -somatostatin, or -glucagon (each, ≅10−11 mol/l). Tracer binding was determined from differences between influx and efflux radioactivity. Saturable binding was observed for insulin and somatostatin, but not for glucagon. Binding in the absence of unlabelled peptides was significantly higher during retrograde perfusion than during anterograde perfusion for insulin (25.9±2.6 vs 16.0±2.1%, mean±SD; each, n=4; p〈0.001) and somatostatin (18.4±2.0 vs 13.6±1.2%; each, n=3; p〈0.05). Non-specific binding was similar in both directions. These findings are attributable to endogenous hormones acting as unlabelled ligands competing with the tracers during anterograde perfusion. This conclusion was supported by the demonstration that endogenous insulin stimulation by d-glucose, but not by l-glucose, caused a decrease in labelled insulin binding only during anterograde perfusion. Displacement curves obtained during retrograde perfusion showed that interstitial concentrations of insulin and somatostatin were 7.5×10−9 and 1.1×10−9 mol/l, respectively. Thus, the exocrine pancreas is indeed exposed to locally high concentrations of islet hormones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400628
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  • 72
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    Electronic Resource
    The role of insulin in clustering of serum lipids and blood pressure in children and adolescents (1995)
    Springer
    Diabetologia 38 (1995), S. 1042-1050 
    Details
    ISSN: 1432-0428
    Keywords: Insulin ; longitudinal ; clustering ; children ; adolescents ; serum lipoproteins ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In adults hyperinsulinaemia is associated with an atherogenic risk profile including obesity, low levels of HDL-cholesterol, high levels of triglycerides and elevated blood pressure. To examine these associations in the young we studied the cross-sectional relationships of insulin with obesity indices (body mass index, subscapular skinfold thickness), serum lipids and blood pressure in 1,865 children, adolescents and young adults aged 6–24 years. We also used longitudinal data to study the value of a single insulin measurement to predict high risk factor levels and clustering of multiple risk factors after a 6-year follow-up. In cross-sectional analyses the levels of triglycerides, HDL-cholesterol, systolic blood pressure and obesity indices were usually significantly different across the quartiles of fasting insulin in both sexes among children, adolescents and young adults. In general, no associations were seen with total cholesterol or LDL-cholesterol. In prospective analysis elevated baseline insulin was related to the incidence of hypertriglyceridaemia (≥95th percentile) at the follow-up. This relationship persisted even after adjustments for baseline obesity or 6-year change in obesity status. Moreover, baseline insulin concentration was higher in subjects who subsequently showed clustering of high triglycerides, low HDL-cholesterol and high systolic blood pressure levels at the follow-up. We conclude that high fasting insulin levels measured in children and adolescents predict the development of hypertriglyceridaemia years later. In addition, high insulin levels seem to precede the development of a potentially atherogenic risk factor profile including low HDL-cholesterol, high triglycerides and high systolic blood pressure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402173
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  • 73
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    Electronic Resource
    Demonstration of a relatively hepatoselective effect of covalent insulin dimers on glucose metabolism in dogs (1995)
    Springer
    Diabetologia 38 (1995), S. 1007-1013 
    Details
    ISSN: 1432-0428
    Keywords: Insulin ; insulin analogues ; glucose metabolism ; euglycaemic clamp ; insulin action ; hepatoselectivity ; glucose production
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin analogues with relatively greater effect on hepatic glucose production than peripheral glucose disposal could offer a more physiological approach to the treatment of diabetes mellitus. The fact that proinsulin exhibits this property to a minor degree may suggest that analogues with increased molecular size may be less able than insulin to obtain access to peripheral receptor sites. Covalent insulin dimers have previously been shown to possess lower hypoglycaemic potencies than predicted by their in vivo receptor binding affinities. Reduced rates of diffusion to peripheral target tissues-might be an explanation for the lower in vivo potency compared to insulin. To test the relative hepatic and peripheral effects of covalent insulin dimers, glucose clamp procedures with D-[3-3H] glucose tracer infusions were used in anaesthetised greyhounds to establish dose-response curves for rates of hepatic glucose production and glucose disposal with insulin, NαB1, NαB′ 1,-suberoyl-insulin dimer, and NεB29, NεB′ 29,-suberoyl-insulin dimer. With NαB1, NαB′ 1,-suberoyl-insulin dimer molar potencies relative to insulin were 68%, (34–133) (mean and 95% fiducial limits), for inhibition of hepatic glucose production and 14.7%, (10.3–20.9) for glucose disposal. With NεB29,NεB′ 29,-suberoyl-insulin dimer potencies were 75%, (31–184) and 2.5%, (1.5–4.3), for inhibition of hepatic glucose production and for glucose disposal, respectively. The demonstration that both dimers exhibit a significantly greater effect on glucose production than on glucose disposal supports the suggestion that analogues with increased molecular size may exhibit reduced ability to gain access to peripheral target cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402169
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  • 74
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    Electronic Resource
    Insulin increases cyclic nucleotide content in human vascular smooth muscle cells: a mechanism potentially involved in insulin-induced modulation of vascular tone (1995)
    Springer
    Diabetologia 38 (1995), S. 936-941 
    Details
    ISSN: 1432-0428
    Keywords: Insulin ; arterial hypertension ; vasodilation ; vascular smooth muscle cells ; cyclic adenosine monophosphate ; cyclic guanosine monophosphate ; nitric oxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It has been suggested that insulin exerts a vasodilating effect, but the mechanisms involved are not completely understood. Since cyclic nucleotides mediate the vasodilation induced by endogenous substances, such as prostacyclin and nitric oxide, we aimed to investigate the influence of insulin (concentration range 240–960 pmol/l) on both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) content in human vascular smooth muscle cells. Insulin dose-dependently increased both nucleotides (cAMP: from 0.7±0.1 to 2.6±0.4 pmol/106 cells, p=0.0001; cGMP: from 1.3±0.2 to 3.4±0.7 pmol/106 cells, p=0.033). This increase is receptor-mediated, since it was blunted when cells were preincubated with the tyrosine kinase inhibitor genistein. The effect of insulin remained significant (p=0.0001) when preincubation with the phosphodiesterase inhibitor theophylline prevented cyclic nucleotide catabolism. The increase of cGMP was blunted when the cells were preincubated with the guanylate cyclase inhibitor methylene blue, and with the nitric oxide-synthase inhibitor NG-monomethyl-l-arginine. At all the concentrations tested, insulin potentiated the increase of cAMP induced by the stable prostacyclin analogue Iloprost (p=0.0001), whereas only at 1920 pmol/l did it potentiate the cGMP increase induced by glyceryltrinitrate (p=0.05). This study demonstrates that the vasodilating effects exerted by insulin may at least in part be attributable to an increase of both cGMP and cAMP via a receptor-mediated activation of adenylate and guanylate cyclases in human vascular smooth muscle cells and that the insulin effect on cGMP is mediated by nitric oxide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400582
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    Electronic Resource
    Regulation of fibronectin by platelet-derived growth factors in cultured rat thoracic aortic smooth muscle cells (1995)
    Springer
    Journal of biomedical science 2 (1995), S. 63-69 
    Details
    ISSN: 1423-0127
    Keywords: Platelet-derived growth factors ; Fibronectin ; Vascular smooth muscle cells ; Insulin ; Insulin-like growth factor-I ; Fibronectin mRNA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Induction of Fibronectin (FN) gene expression by platelet-derived growth factor (PDGF) isoforms in rat thoracic aortic smooth muscle cells (SMC) was examined. PDGF-BB enhances FN levels in SMC cultures in a time- and concentration-response fashion. PDGF-AA and PDGF-AB show no effect on FN levels. The effects of insulin and insulin-like growth factor-I (IGF-I) on PDGF-BB-induced FN levels were examined. No additivity of FN levels is observed between PDGF-BB and insulin and/or IGF-I. Experiments also show that PDGF-BB enhances FN mRNA levels, implying that acquisition of additional FN mRNA units accounts for the increase in FN levels. Induction of FN and FN mRNA levels by PDGF-BB could be one of the initial events in vascular SMC proliferation and extracellular matrix expansion, leading to atherosclerosis and hypertension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02257927
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  • 76
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    Reduced pancreatic insulin release and reduced peripheral insulin sensitivity contribute to hyperglycaemia in cystic fibrosis (1995)
    Springer
    European journal of pediatrics 154 (1995), S. 356-361 
    Details
    ISSN: 1432-1076
    Keywords: Key words Cystic fibrosis ; Diabetes ; Insulin secretion ; Insulin ; resistance ; Minimal model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Traditional opinion holds that patients with cystic fibrosis (CF) develop impaired glucose tolerance or diabetes due to insulinopenia caused by fibrosis of the pancreas. However, studies on the dynamics of insulin secretion and peripheral insulin action have yielded conflicting results. We studied 18 patients with CF (9 ♂, 9 ♀, age 15–29 years) and 17 healthy control subjects (8 ♂, 9 ♀, 20–32 years). Oral glucose tolerance tests and combined i.v.-glucose-tolbutamide-tests were performed on separate days in fasting subjects. Bergman's "Minimal Model" was used to quantitate both peripheral insulin sensitivity (SI) and insulin-independent glucose disposal (glucose effectiveness; SG). Based on National Diabetes Data Group criteria, 4 patients were classified as diabetic (22%; CF-DM), 3 patients (17%) had impaired glucose tolerance (CF-IGT) while glucose metabolism was normal in 11 patients (61%; CF-NGT). Irrespective of the degree of glucose tolerance, the insulin response to oral glucose was not reduced but delayed, up to 60 min in the CF-IGT/DM group. First-phase insulin release (0–10 min) after i.v.-glucose was significantly lower in CF patients (29% of healthy controls; P 〈 0.0001), with no difference between the CF-NGT and CF-IGT/ DM groups. Insulin release following tolbutamide injection was only marginally reduced in CF patients (64% of controls). In contrast, SI was significantly reduced in the subgroup of CF patients with abnormal glucose metabolism (CF-IGT/DM: 0.97 ± 0.16 · 10–4 l/min/pmol; control group: 1.95 ± 0.25; P 〈 0.05). Conclusion The early insulin release is reduced in response to i.v.-glucose, while in the oral glucose tolerance test, insulin secretion is quantitatively preserved, but delayed. Reduced peripheral insulin sensitivity is a major factor for impaired glucose tolerance and diabetes mellitus in CF patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310050303
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    Early metabolic treatment after liver transplant: Amino acid tolerance (1995)
    Springer
    Intensive care medicine 21 (1995), S. 802-807 
    Details
    ISSN: 1432-1238
    Keywords: Liver transplant ; Early postoperative phase ; Glucose ; Insulin ; Amino acid tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective We investigated the amino acid (AA) tolerance during Total Parenteral Nutrition (TPN) in adult patients undergone liver transplant (LTX). Design The treatment (Glucose and AA), induced on the 2nd postoperative day, was later maintained with 27 kcal/kg Ideal Body Weight (IBW) as glucose and 0.12 (12 patients: protocol #1), 0.18 (10 patients: protocol #2) and 0.25 g nitrogen (N)/kg IBW (13 patients: protocol #3) till end of the 6th postoperative day. The N intake was sequentially modified in protocol #2 and #3 to increase the supply of the amino acid (AA) that resulted in an infusion plasma level below the expected “normal” range (between 1 and 1.6 times the overnight fasting plasma level of volunteer). Patients 35 consecutive adult patients without diabetes and organ failures for the entire study period.Measurements: Plasma AA profile was measured before LTX and at the last TPN day under continuous infusion. During #1 and #2 protocol, many AA resulted below or at the lower range of the norm while, during 0.25 gN/kg IBW infusion, the majority of the administered AA significantly increased with respect to reference values. Nevertheless, they remained in the “normal” plasma range indicating that they were supplied in an optimal amount (particularly the aromatic and sulphurated ones, potentially toxic if liver function is impaired, and the branched chain AA (BCAA) given at consistent dosage: 0.5 g/kg). Arginine resulted significantly increased (Arg: 1.9 times the reference) and cystine (Cys: 0.45), serine (Ser: 0.8) and taurine (Tau: 0.85) remained significantly lower than “normal” as well as the not administered citrulline (Cit: 0.58) and alfa amino butyric acid (Aba: 0.41). The AA (and calorie) load almost balanced the N losses during the 5th (0.411±0.038) and 6th study day (0.305±0.019 gN/kg). Conclusions 0.25 gN/kg could be considered the minimum N load in the uncomplicated adult LTX recipients, for reassuring a balanced plasma AA pattern and body N turnover in the early postoperative phase.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01700962
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  • 78
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    A double-blind, randomized, placebo-controlled, multi-center study of brofaromine in the treatment of post-traumatic stress disorder (1995)
    Springer
    Psychopharmacology 122 (1995), S. 386-389 
    Details
    ISSN: 1432-2072
    Keywords: Brofaromine ; MAOI ; PTSD ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A large multi-center, double-blind, parallel trial to assess the efficacy of brofaromine in the treatment of post traumatic stress disorder (PTSD) failed to show a significant difference between the brofaromine and placebo treatment groups. The placebo response rate in this study was higher than that in previously published double-blind, placebo-controlled studies of PTSD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246271
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  • 79
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    Effects of neuropeptide Y, insulin, 2-deoxyglucose, and food deprivation on food-motivated behavior (1995)
    Springer
    Psychopharmacology 120 (1995), S. 267-271 
    Details
    ISSN: 1432-2072
    Keywords: Neuropeptide Y ; Insulin ; 2-Deoxyglucose ; Food deprivation ; Motivation ; Reinforcer efficacy ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The current study demonstrates the ability of neuropeptide Y (NPY) to increase break points under a progressive ratio 1 (PR1) reinforcement schedule. An initial response resulted in delivery of a food reinforcer (45 mg pellet) under the PR1, and an additional response was required foreach successive reinforcer. The break point, the number of responses emitted to obtain the last reinforcer, is considered a measure of reinforcing efficacy or motivational strength of the food reinforcer. NPY (0.3–10 µg) significantly increased break point to levels comparable to those produced by 36–48 h of food deprivation. Although insulin (3–8 U/kg) and 2-deoxyglucose (150–250 mg/kg) also increased food intake, neither increased break points to levels produced by NPY or food deprivation. These data suggest that NPY may change the value of food in ways that cannot be accounted for by changes in insulin, glucose levels or intracellular glucoprivation. These results emphasize that simply measuring the amount of freely available food eaten is not a fully adequate measure of the strength of the feeding behavior.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02311173
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  • 80
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    Relation between extracellular [K+], membrane potential and contraction in rat soleus muscle: modulation by the Na+-K+ pump (1995)
    Springer
    Pflügers Archiv 430 (1995), S. 909-915 
    Details
    ISSN: 1432-2013
    Keywords: Na+-K+ pump ; Potassium ; Salbutamol ; Insulin ; Skeletal muscle ; Fatigue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An increased extracellular K+ concentration ([K+]0) is thought to cause muscle fatigue. We studied the effects of increasing [K+]0 from 4 mM to 8–14 mM on tetanic contractions in isolated bundles of fibres and whole soleus muscles from the rat. Whereas there was little depression of force at a [K+]0 of 8–9 mM, a further small increase in [K+]0 to 11–14 mM resulted in a large reduction of force. Tetanus depression at 11 mM [K+]o was increased when using weaker stimulation pulses and decreased with stronger pulses. Whereas the tetanic force/resting membrane potential (E M) relation showed only moderate force depression with depolarization from −74 to −62 mV, a large reduction of force occurred whenE M fell to −53 mV. The implications of these relations to fatigue are discussed. Partial inhibition of the Na+-K+ pump with ouabain (10−6 M) caused additional force loss at 11 mM [K+]0. Salbutamol, insulin, or calcitonin gene-related peptide all stimulated the Na+-K+ pump in muscles exposed to 11 mM [K+ 0] and induced an average 26–33% recovery of tetanic force. When using stimulation pulses of 0.1 ms, instead of the standard 1.0-ms pulses, force recovery with these agents was 41–44% which was significantly greater (P 〈 0.025). Only salbutamol caused any recovery ofE M (1.3 mV). The observations suggest that the increased Na+ concentration difference across the sarcolemma, following Na+-K+ pump stimulation, has an important role in restoring excitability and force.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01837404
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  • 81
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    Regulatory volume decrease in a renal distal tubular cell line (A6) II. Effect of Na+ transport rate (1995)
    Springer
    Pflügers Archiv 430 (1995), S. 945-953 
    Details
    ISSN: 1432-2013
    Keywords: A6 epithelia ; Regulatory volume decrease ; Quinine ; Ba2+ ; Ouabain ; Insulin ; K+ channels ; Hypotonicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A6 epithelia, a cell line originating from the distal tubular part of the kidney ofXenopus laevis, were cultured on permeable supports and mounted in an Ussing-type chamber. Cell thickness (T c), short-circuit current (I sc) and transepithelial conductance (G t) were recorded while tissues were bilaterally incubated in NaCl solutions and the transepithelial potential was clamped to zero. Effects of inhibition and stimulation of transepithelial Na+ transport on cell volume and on its regulation during a hyposmotic challenge were investigated. Under control conditions a slow spontaneous decrease ofT c described by a linear baseline was recorded. The reduction of the apical osmolality from 260 to 140 mosmol/kg did not alter cell volume significantly, demonstrating a negligible water permeability of the apical barrier. The inhibition of Na+ uptake by replacing apical Na+ byN-methyl-d-glucamine (NMDG+) did not affect cell volume under isotonic conditions. An increase ofT c by 12.1% above the control baseline was recorded after blocking active transport with ouabain for 60 min. The activation of Na+ transport with insulin or oxytocin, which is known to activate the apical water permeability in other epithelia, did not alter cell volume significantly. The insensitivity of cell volume to alterations in apical Na+ uptake or Na+ pump rate confirms the close coupling between apical and basolateral transport processes. The blockage of basolateral K+ channels by 5 mM Ba2+ elicited a significant increase inT c of 16.3% above control. Quinine, a potent blocker of volume-activated K+ channels, did not changeT c significantly. Basolateral hypotonicity elicited a rapid rise inT c followed by a regulatory volume decrease (RVD). An RVD was also recorded after blocking apical Na+ uptake as well as after stimulating apical Na+ uptake with oxytocin or insulin. Inhibition of active transport with ouabain as well as blocking K+ efflux at the basolateral side with Ba2+ or quinine abolished the RVD. The inhibition of the RVD by ouabain seems to be caused by a depletion of cellular K+, whereas the effects of Ba2+ and quinine are most likely due to the blockage of the basolateral K+ pathway.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01837408
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    Abrupt discontinuation of cycled parenteral nutrition is safe (1995)
    Springer
    Diseases of the colon & rectum 38 (1995), S. 933-939 
    Details
    ISSN: 1530-0358
    Keywords: Nutrition ; Insulin ; Glucose ; Inflammatory bowel disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Abrupt discontinuation of total parenteral nutrition (TPN) has been recommended but is not widely practiced because of fear of hypoglycemia. METHODS: To determine whether hormonal counterregulatory mechanisms prevent hypoglycemia, we studied 12 patients (10 with inflammatory bowel disease, of which 6 received dexamethasone) after both abrupt and tapered discontinuation of 3∶1 TPN solution in a clinical research facility. Venous blood was drawn before reduction of TPN rate in the tapered group or 15 minutes before and at abrupt discontinuation in the abrupt group and every 15 minutes for 1.5 hours. RESULTS: Glucose decreased from 152±56 (baseline) to 100±22 mg/dl 90 minutes after gradual discontinuation of TPN, compared with 135±45 to 96±15 mg/dl at 90 minutes after abrupt discontinuation, with no significant differences in mean glucose values. Mean epinephrine, norepinephrine, insulin, glucagon, growth hormone, cortisol, symptom score, and vital signs were not statistically different between the two groups. DISCUSSION: Hypoglycemia does not occur after abrupt discontinuation of TPN. The same changes in counterregulatory hormones were seen whether discontinuation was tapered or abrupt. In stable patients, TPN solutions can be abruptly discontinued.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02049728
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  • 83
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    Kinetic of body nitrogen loss during a whole day infusion and withdrawal of glucose and insulin in injured patients (1995)
    Springer
    Intensive care medicine 21 (1995), S. 447-451 
    Details
    ISSN: 1432-1238
    Keywords: Injury ; Glucose ; Insulin ; N kinetic ; 3-methylhistidine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective To investigate the kinetics of body nitrogen (N) excretion during 24 h glucose infusion (relating glycemia with insulin supply) and during subsequent 24 h saline infusion in injured patients during a full blown stress reaction. To define the lag time between the start or the withdrawal of glucose and insulin infusion, and the modification in the N loss from the body, and the time span to reach the maximum effect and its size. The knowledge of these variables is mandatory to plan short term studies in critically ill patients, while assuring the stability of the metabolic condition during the study period, and also to assess the possible weaning of the effect on protein breakdown during prolonged glucose and insulin infusion. Design 24–36 h after injury, patients were fasted (〈100 g glucose) for 24 h (basal day). Thereafter, a 24 h glucose infusion in amount corresponding to measured fasting energy production rate (EPR), clamping glycemia at normal level with insulin supply followed by 24 h saline infusion, was performed. Total N, urea and 3-methyl-histidine (3-MH) in urine were measured on 4 h samples starting from 20th h of the basal day. Setting Multipurpose ICU in University Hospital. Patients 6 consecutive patients who underwent accidental and/or surgical injury, immediately admitted for respiratory assistance (FIO2〈0.4). Excluded patients were those with abnormal nutritional status, cardiovascular compromise and organ failures. Main results Patients showed a 33% increase in measured versus predicted fasting EPR and a consistent increase in N and 3-MH urinary loss. An infusion of glucose at 5.95±0.53 mg/kg·min (97.20±0.03% of the fasting measured EPR) with 1.22±0.18 mU/kg·min insulin infusion reduced N and 3-MH loss after a time lag of 12 h. The peak decrease in body N (−36%) and 3-MH loss (−38%) was reached during the first 12 h of glucose withdrawal period. Thereafter, during the following 12 h, the effect completely vanished confirming that it is therapy-dependent and that the metabolic environment of the patients did not change during the three days study period. Conclusion 24 h glucose withdrawal reduces N and 3-MH loss in injured patients, the drug-like effect is maintained during the first 12 h of withdrawal and thereafter disappears. The study suggests that at least a 24 h study period is necessary when planning studies exploring energy-protein metabolism relationship in injured patients, and, again 24 h before changing protocol in a crossover study.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01707416
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    Chick embryo retina development in vitro: The effect of insulin (1995)
    Springer
    Neurochemical research 20 (1995), S. 803-813 
    Details
    ISSN: 1573-6903
    Keywords: Insulin ; chick embryo ; retina ; in vitro development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this paper we study the development of chick embryo retina culturedin vitro and the effects exerted by insulin. Retinas were removed from 7-day embryos and cultured in serum-and hormone-free medium for 7 additional days. Under these conditions retinal cells survived and underwent cholinergic differentiation, as previously ascertained by Hausman et al. (Dev. Brain Res., 1991, 59: 31–37). However, a great retardation of development was noted compared to uncultured control, 14-day retina. In fact both wet weight and DNA and protein content increased much slower than in ovo and the tubulin content decreased below even the starting value. In addition, although after 7 days in culture retinal cells were organized in identifiable layers, nevertheless the typical organization equivalent to 14-day in ovo retina was absent. The addition of insulin in the medium markedly increased the wet weight of cultured retinas, their protein content and the level of tubulin pools, particularly that of non-assembled fraction. Nevertheless insulin did not modify DNA synthesis and did not induce the increment of both neuron specific enolase and actin. Morphological observations show that insulin markedly increased the number and the thickening of the fiber layers. These results, together with the facts that retina synthesizes and secretes insulin and possesses specific insulin receptors suggest that insulin can have autocrine or paracrine regulatory functions in retinal development by exerting a general effect on retinal growth and a more specific one on tubulin production.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00969692
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    Insulin-like growth factor I levels decrease in the development of diabetes inMacaca nigra (1995)
    Springer
    Primates 36 (1995), S. 423-429 
    Details
    ISSN: 0032-8332
    Keywords: Macaca nigra ; Diabetes ; Insulin ; IGF-I
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Members of the monkey speciesMacaca nigra spontaneously develop impairments in insulin secretion and glucose clearance, and eventually become overtly diabetic. Changes in certain metabolic signals such as clearance of glucose and insulin increment secreted in an intravenous glucose tolerance test have allowed the identification of four stages in the progression from non-diabetes to diabetes in monkeys — non-diabetic, hormonally impaired, borderline diabetic, and diabetic. Recently, another metabolic stage, hyperinsulinemic, was also identified in these animals. In recent years, other factors besides those listed above have been implicated to be correlated with the metabolic progression from a nondiabetic to a diabetic state. One of these factors, is insulin like growth factor I (IGF-I). In diabetic humans who are in poor metabolic control, and in rats with streptozotocin induced ketotic diabetes, serum levels of IGF-I are lowered by as much as 40–50% of control non-diabetics. If indeed decreased IGF-I levels are correlated with the onset of diabetes then changes in IGF-I concentrations prior to the clinically diagnosed disease state would be expected. Using serum samples collected from different animals in a colony ofMacaca nigra in a variety of metabolic states, we have found that IGF-I and insulin levels decrease in each defined metabolic state as the animals progress from nondiabetic to diabetic. Since IGF-I and insulin levels decrease in a similar fashion in the progression of this disease then this maybe indicative of the coordinate expression of these two factors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02382864
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  • 86
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    Zur reagibilität von kortikalen Knochenkapillaren (1995)
    Springer
    Langenbeck's archives of surgery 380 (1995), S. 176-183 
    Details
    ISSN: 1435-2451
    Keywords: Cortical bone ; Capillaries ; Endothelium ; Epinephrine ; ATP ; Insulin ; Transmission electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Es sollte herausgefunden wurden, ob vasoaktive Pharmaka morphologische Veränderungen in kortikalen Knochenkapillaren machen können. Dazu erhielten Swiss-Mäuse i.v.-Bolusinjektionen von Adrenalin, ATP and Insulin. Eine Kontrollgruppe blieb unbehandelt; einer anderen wurde isotonische Kochsalzlösung injiziert. Alle Tiere wurden in gleicher Weise gehandhabt: Das mittlere Stück der Tibiadiaphyse wurde reseziert and für die TEM aufgearbeitet. Die Lumina and die Endothelien der Kapillaren wurden morphometriert. Dabei fanden sich einige signifikante Unterschiede: Adrenalin vergrößert sowohl die Lumenweite als auch die Endotheldicke. ATP verdünnt das Endothel. Insulin (die Hypoglykämie?) verdickt das Endothel. Diese Befunde begründen einige physiologische Hypothesen: Die Adrenalineffekte könnten eine Verkleinerung des Extravasalraums and ein intraossäres Ödem bedeuten, was die Diffusionszeit von Mineralien verlängerte. Der intrakortikale Perfusionsdruck nähme ab and die Perfusionsrate des Knochens stiege. ATP würde die Diffusionszeit reduzieren and den Extravasalraum vergrößern. Offenbar haben Kapillaren auch im Knochengewebe spezifische Insulinrezeptoren.
    Notes: Abstract In order to study any morphological effects that vasoactive drugs might exert on cortical bone capillaries, Swiss mice received one intravenous bolus injection each of epinephrine, ATP and insulin. In one control group saline solution was injected and another was not treated. All animals were handled in the same way. A piece of the tibia diaphysis was resected and prepared for transmission electron microscopy (TEM). The lumina and the endothelia of capillaries were submitted to computerized morphometry. Some significant changes were noted: epinephrine increases both the width of the lumen and the endothelium. ATP decreases the endothelium. Insulin (hypoglycaemia?) thickens the endothelium. These finding suggest some physiological hypotheses: the epinephrine-induced widening of the lumen and the thickening of the endothelium might reflect a decreased extravasal space and oedema of cortical bone that might cause the diffusion of minerals to take longer. Intracortical perfusion pressure would then decrease and the bone perfusion rate increase. ATP might reduce the transcapillary diffusion time and increase the extravasal space in cortical bone. Apparently there are specific insulin receptors in cortical bone capillaries.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00207726
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    Inhibitory effects of suramin on androgen-dependent and-independent growth of neonatal mouse seminal vesicles in vitro (1995)
    Springer
    Urological research 23 (1995), S. 127-133 
    Details
    ISSN: 1434-0879
    Keywords: Seminal vesicle ; Suramin ; Androgen ; Insulin ; Organ culture ; Epithelial growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of suramin on the growth of seminal vesicles (SVs) of neonatal mice were investigated in vitro. SVs from 0-day-old male mice were cultured in serum-free chemically defined medium supplemented with 5α-dihydrotestosterone (DHT, 10-8 M) and insulin (10 μg/ml), alone and in combination. Prior to culture. SVs from 0-day-old mice had no epithelial branches. SVs cultured in medium with DHT formed numerous epithelial branches, while epithelial branching did not occur in SVs cultured without DHT. The addition of suramin (0.2 mM) to medium containing DHT inhibited the formation of epithelial branches almost completely. Removal of suramin from the medium on days 2, 4, and 6 of culture initiated the formation of epithelial branches. Suramin (0.2 mM) reversibly decreased 3H-thymidine-labeling indices (3H-LI) of both epithelium and mesenchyme of SVs cultured in medium with DHT plus insulin or DHT alone during 8 days of culture. Suramin also decreased 3H-LI of both epithelium and mesenchyme of SVs cultured in medium with insulin alone. The present study indicates that suramin reversibly inhibits not only androgen-dependent but also androgen-independent growth and ductal branching morphogenesis of neonatal mouse SVs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00307943
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  • 88
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    Studies on insulin-like growth factor-I and insulin in chick limb morphogenesis (1995)
    New York, NY [u.a.] : Wiley-Blackwell
    Developmental Dynamics 202 (1995), S. 67-79 
    Details
    ISSN: 1058-8388
    Keywords: IGF-I ; Insulin ; Limb development ; Apical ectodermal ridge ; Msx2 ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The apical ectodermal ridge (AER) promotes the proliferation and directed outgrowth of the subridge mesodermal cells of the developing limb bud, while suppressing their differentiation. Insulin-like growth factor-I (IGF-I) and its receptor are expressed by the subridge mesodermal cells of the chick limb bud growing out in response to the AER, and specific insulin receptors are present in the limb bud during its outgrowth. To study the possible roles of IGF-I and insulin in limb outgrowth, we have examined their effects on the morphogenesis of posterior and anterior portions of the distal tip of stage 25 embryonic chick wing buds subjected to organ culture in serum-free medium in the presence or absence of the AER and limb ectoderm. The distal mesoderm of control posterior explants lacking an AER or all limb ectoderm ceases expressing IGF-I mRNA, exhibits little or no proliferation, fails to undergo outgrowth, and rapidly differentiates. Exogenous IGF-I and insulin promote the outgrowth and proliferation and suppress the differentiation of distal mesodermal cells in posterior explants lacking an AER or limb ectoderm, thus mimicking at least to some extent the outgrowth promoting and antidifferentiative effects normally elicited on the subridge mesoderm by the AER. Furthermore, IGF-I and insulin-treated posterior explants exhibit high IGF-I mRNA expression, indicating that IGF-I and insulin maintain the expression of endogenous IGF-I by the subridge mesoderm. We have also found IGF-I and insulin can affect the morphology and activity of the AER. When the posterior portion of the wing bud tip is cultured with the AER intact in control medium, on day 4-5 the AER flattens, ceases expressing high amounts of the AER-characteristic homeobox-containing gene Msx2, and concomitantly an elongated cartilaginous element differentiates in the subridge mesoderm. In contrast, in the presence of exogenous IGF-I or insulin the AER of such explants does not flatten, continues expressing high amounts of Msx2, and the subridge mesoderm remains undifferentiated and proliferative. Thus, exogenous IGF-I and insulin maintain the thickness of the AER and sustain its expression of Msx2, while sustaining the anti-differentiative effect normally elicited on the subridge mesoderm by a thickned functional AER. Notably, we have also found that exogenous IGF-I and insulin induce the formation of a thickened ridge-like structure that expresses high amounts of Msx2 from the normally thin distal anterior ectoderm of the limb bud, while promoting dramatic outgrowth and proliferation of the anterior mesoderm, which normally undergoes little outgrowth or proliferation. These studies provide support for the hypothesis that endogenous IGF-I and insulin may be involved in promoting the outgrowth and suppressing the differentiation of limb mesoderm in response to the AER, and also in regulating and/or maintaining at least some aspects of AER activity. © 1995 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aja.1002020107
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  • 89
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    Endocytosis in mouse blastocysts: Characterization and quantification of the fluid phase component (1995)
    New York, NY [u.a.] : Wiley-Blackwell
    Molecular Reproduction and Development 41 (1995), S. 225-231 
    Details
    ISSN: 1040-452X
    Keywords: Insulin ; Pinocytosis ; Embryo ; Protein ; Regulation ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: Fluid phase endocytosis in mouse blastocysts was characterized using the fluid phase marker, 3H-dextran, which did not bind to the membrane. This nonsaturable uptake occurred via an energy-requiring process, with only 20% accountable by diffusion as indicated by analysis at 4°C. Insulin stimulated uptake of 3H-dextran by 30% (P〈0.05) over the first hr. The rate of uptake then decreased in both control and insulin-treated blastocysts. However, by 2 hr, insulin-treated blastocysts contained 38% more 3H-dextran (38%; P〈0.01) than control blastocysts. Incubation of blastocysts in protein-free medium increased 3H-dextran uptake to a rate equivalent to 12% of the blastocyst volume/min (1,500 ± 240 pliter/hr), compared to 4.5% and 1.5% of the blastocyst volume/min for uptake in the presence of 0.1 g BSA/I and 10 g BSA/I, respectively. Confocal microscopic studies of fluorescently labelled dextran uptake in blastocysts, cultured in the absence of BSA, showed an increase in weak fluorescence labelling in the trophectoderm cells of blastocysts, compared to blastocysts cultured in the presence of BSA. There was no diffusion of fluorescence label into the blastocoel cavity. This is consistent with fluid being endocytosed, possibly by a large number of small pinocytic vesicles. Thus fluid-phase endocytosis in blastocysts is stimulated by insulin, increasing the delivery of nutrient-containing fluid into blastocysts. In the absence of protein, embryos also increase fluid uptake, possibly in an attempt to maintain the rate of supply of protein nutrient to trophectoderm cells. An analysis of the rate of protein delivery in both adsorbed and dissolved phases is presented, which reveals the potential for significant contributions of both phases of endocytosis to blastocyst metabolism in vivo. © 1995 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
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    URL: http://dx.doi.org/10.1002/mrd.1080410213
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  • 90
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    Mouse embryonic stem cells express receptors of the insulin family of growth factors (1995)
    New York, NY [u.a.] : Wiley-Blackwell
    Molecular Reproduction and Development 42 (1995), S. 173-179 
    Details
    ISSN: 1040-452X
    Keywords: Embryonic stem cells ; Insulin ; IGF-I ; IGF-II ; Receptor ; RT-PCR ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: Insulin and insulin-like growth factors (IGF-I and -II) are members of a family of growth factors which are known to be developmentally regulated during preimplantation mouse embryogenesis. The physiological actions of the insulin family of growth factors are mediated by interactions with specific cell surface receptors that are detectable on the cells of preimplantation mouse embryos. Mouse embryonic stem (ES) cells are totipotent cells derived directly from the inner cell mass of the blastocyst. ES cells have the ability to differentiate into all three germ layers and have unlimited growth potential under certain culture conditions. The great advantage of ES cells is the ability to obtain large amounts of tissue for biochemical studies as compared with preimplantation embryos. To examine in greater detail the biological actions of the insulin family of growth factors, the expression of their cognate receptors on ES cells was examined. ES cells were cultured in DMEM medium supplemented with leukemia inhibitory factor (LIF) to maintain the undifferentiated state. Receptor expression was evaluated at the mRNA level using the reverse transcription polymerase chain reaction (RT-PCR), and at the protein level by radioactive labeled ligand-receptor binding assay. Using RT-PCR, mRNAs of all three growth factor receptors were detected in ES cells. Messenger RNA from ES cells was reverse transcribed into cDNA by AMV reverse transcriptase at 42°C for 1 hr. The reverse transcription reaction was amplified with Taq polymerase and specific primers for insulin, IGF-I, or IGF-II receptors by PCR. RT-PCR and the control plasmid cDNA PCR products were resolved electrophoretically on 3% agarose gels. Each amplified PCR product showed the predicted correct size. The target sequence of RT-PCR amplified fragments were further verified by restriction enzyme digestion. The expression of receptors at the protein level was confirmed by Scatchard analysis, which showed specific binding of the radiolabeled ligands. This study shows that ES cells may provide a useful model to study the biological actions of the insulin family growth factors. © 1995 wiley-Liss, Inc.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/mrd.1080420206
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  • 91
    Electronic Resource
    Electronic Resource
    Functions of proteins secreted by oviduct epithelial cells (1995)
    New York, NY [u.a.] : Wiley-Blackwell
    Microscopy Research and Technique 32 (1995), S. 1-12 
    Details
    ISSN: 1059-910X
    Keywords: Spermatozoon ; Fertilization ; Embryo ; Growth factors ; Insulin ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Natural Sciences in General
    Notes: Studies on embryonic development in vitro as well as observations in vivo, suggested that two aspects of oviduct physiology are important for early development. On one side has to be considered the oviduct “environment”: temperature, pH, osmotic pressure, nutrients, oxygen tension, free radical scavengers, etc. On the other, the oviduct “active components”: stimulatory and/or regulatory molecules, supposed to finely regulate the fertilisation process and the first differentiative steps.While the physical environment of the oviduct has been under investigation for some decades, studies on oviduct-specific molecules and their functions have only been developed much more recently. The amount of information on this topic, however, has rapidly reached the size that demands a summary.In this review the descriptive literature on oviduct specific proteins will be examined as a basis for illustrating the possible functions of these molecules. In particular their role in fertilisation and early embryonic cleavages will be analysed in some details. Finally a section is devoted to the presence and physiological significance of growth factors in oviduct fluid. © 1995 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jemt.1070320102
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  • 92
    Electronic Resource
    Electronic Resource
    Development of a serum-free culture medium for the large scale production of recombinant protein from a Chinese hamster ovary cell line (1995)
    Springer
    Cytotechnology 17 (1995), S. 153-163 
    Details
    ISSN: 1573-0778
    Keywords: Insulin ; ferric citrate ; Chinese hamster ovary ; dhfr ; serum-free
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract A serum-free medium, WCM5, has been developed for the large scale propagation of CHO (Chinese hamster ovary) cells which express recombinant protein using dihydrofolate reductase as a selectable marker. WCM5 was prepared by supplementing Iscoves medium without lecithin, albumin or transferrin with a number of components which were shown to benefit growth. WCM5 medium contained 5 mg l−1 human recombinant insulin (Nucellin) but was otherwise protein-free. CHO 3D11* cells which had been engineered to express a humanised antibody, CAMPATH*-1H, were routinely grown using serum-containing medium. From a seeding density of 105 cells ml−1, cells grown in static culture with serum reached a maximal cell density of 6.5×105 cells ml−1 after 6 days in culture and produced a maximal antibody concentration of 69 mg l−1 after 11 days in culture. CHO 3D11* cells grown with serum were washed in serum-free medium then cultured in WCM5 medium. Following a period of adaptation the cell growth and product yield was superior to that achieved with serum-containing medium. CHO cells producing CAMPATH-1H grown in an 8000 l stirred bioreactor seeded with 2×105 cells ml−1 reached a maximal viable cell density of 2.16×106 cells ml−1 after 108 h in culture and a maximal antibody concentration of 131.1 mg l−1 after 122 h in culture.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00749653
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  • 93
    Electronic Resource
    Electronic Resource
    Distribution of peptidyl-glycine alpha-amidating monooxygenase immunoreactivity in the brain, pituitary and islet organ of the anglerfish (Lophius americanus) (1995)
    Springer
    Cell & tissue research 280 (1995), S. 159-170 
    Details
    ISSN: 1432-0878
    Keywords: Peptidyl-glycine alpha-amidating monooxygenase ; Insulin ; Glucagon ; Anglerfish peptide Y ; Neuropeptide Y ; Brain, pituitary, and islet organ ; Pancreas ; Immunohistochemistry ; Anglerfish, Lophius americanus (Teleostei)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Peptidyl-glycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) is an enzyme that catalyzes conversion of glycine-extended peptides to alpha-amidated bioactive peptides. Two peptides that are processed at their carboxyl-termini by this enzyme are neuropeptide Y and anglerfish peptide Y, both of which possess a C-terminal glycine that is used as a substrate for amidation. Results from previous reports have demonstrated that neuropeptide Y-like and anglerfish peptide Y-like immunoreactivities are present in the brain of anglerfish (Lophius americanus). Furthermore, neuropeptide Y-like peptides, namely anglerfish peptide Y and anglerfish peptide YG (the homologues of pancreatic polypeptide) are present in the islet organ of this species. Neuropeptide Y has also been localized in the anterior, intermediated and posterior lobes of the pituitary gland in a variety of species. In order to learn more about the distribution of the enzyme responsible for alpha amidation of these peptides in the brain and pituitary and to specifically investigate the relationship of this enzyme to peptide synthesizing endocrine cells of the anglerfish islet, we performed an immunohistochemical study using several antisera generated against different peptide sequences of the enzyme. PAM antisera labeled cells in the islet organ, pituitary and brain, and fibers in the brain and pituitary gland. The PAM staining pattern in the brain was remarkably similar to the distribution of neuropeptide Y immunoreactivity reported previously. Clusters of cells adjacent to vessels in the anterior pituitary displayed punctate PAM immunoreactivity while varicose fibers were observed in the pituitary stalk and neurohypophysis. Endocrine cells of the islet organ were differentially labeled with different PAM antisera. Comparison of the staining patterns of insulin, glucagon, and anglerfish peptide Y in the islet organ to PAM immunoreactivity suggests a distribution of forms of PAM enzyme in insulin and anglerfish peptide Y-containing cells, but no overlap with glucagon-producing cells. The results also indicate that PAM immunoreactivity is widely distributed in the brain, pituitary and islet organ of anglerfish in cells that contain peptides that require presence of a C-terminal glycine for amidation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00304521
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  • 94
    Electronic Resource
    Electronic Resource
    Role of glucose and insulin in regulating glycogen synthase and phosphorylase activities in rainbow trout hepatocytes (1995)
    Springer
    Journal of comparative physiology 165 (1995), S. 62-70 
    Details
    ISSN: 1432-136X
    Keywords: Glycogen ; Hepatocyte ; Insulin ; 13C NMR ; Rainbow trout, Oncorhynchus mykiss
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract This study, using 13C nuclear magnetic resonance spectroscopy showed enrichment of glycogen carbon (C1) from 13C-labelled (C1) glucose indicating a direct pathway for glycogen synthesis from glucose in rainbow trout (Oncorhynchus mykiss) hepatocytes. There was a direct relationship between hepatocyte glycogen content and total glycogen synthase, total glycogen phosphorylase and glycogen phosphorylase a activities, whereas the relationship was inverse between glycogen content and % glycogen synthase a and glycogen synthase a/glycogen phosphorylase a ratio. Incubation of hepatocytes with glucose (3 or 10 mmol·1-1) did not modify either glycogen synthase or glycogen phosphorylase activities. Insulin (porcine, 10-8 mol·1-1) in the medium significantly decreased total glycogen phosphorylase and glycogen phosphorylase a activities, but had no significant effect on glycogen synthase activities when compared to the controls (absence of insulin). In the presence of 10 mmol·1-1 glucose, insulin increased % glycogen synthase a and decreased % glycogen phosphorylase a activities in trout hepatocytes. Also, the effect of insulin on the activities of % glycogen synthase a and glycogen synthase a/glycogen phosphorylase a ratio were more pronounced at low than at high hepatocyte glycogen content. The results indicate that in trout hepatocytes both the glycogen synthetic and breakdown pathways are active concurrently in vitro and any subtle alterations in the phosphorylase to synthase ratio may determine the hepatic glycogen content. Insulin plays an important role in the regulation of glycogen metabolism in rainbow trout hepatocytes. The effect of insulin on hepatocyte glycogen content may be under the control of several factors, including plasma glucose concentration and hepatocyte glycogen content.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00264687
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  • 95
    Electronic Resource
    Electronic Resource
    Distribution of peptidyl-glycine alpha-amidating monooxygenase immunoreactivity in the brain, pituitary and islet organ of the anglerfish (Lophius americanus) (1995)
    Springer
    Cell & tissue research 280 (1995), S. 159-170 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Peptidyl-glycine alpha-amidating monooxygenase ; Insulin ; Glucagon ; Anglerfish peptide Y ; Neuropeptide Y ; Brain ; pituitary ; and islet organ ; Pancreas ; Immunohistochemistry ; Anglerfish ; Lophiusamericanus (Teleostei)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Peptidyl-glycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) is an enzyme that catalyzes conversion of glycine-extended peptides to alpha-amidated bioactive peptides. Two peptides that are processed at their carboxyl-termini by this enzyme are neuropeptide Y and anglerfish peptide Y, both of which possess a C-terminal glycine that is used as a substrate for amidation. Results from previous reports have demonstrated that neuropeptide Y-like and anglerfish peptide Y-like immunoreactivities are present in the brain of anglerfish (Lophius americanus). Furthermore, neuropeptide Y-like peptides, namely anglerfish peptide Y and anglerfish peptide YG (the homologues of pancreatic polypeptide) are present in the islet organ of this species. Neuropeptide Y has also been localized in the anterior, intermediate and posterior lobes of the pituitary gland in a variety of species. In order to learn more about the distribution of the enzyme responsible for alpha amidati on of these peptides in the brain and pituitary and to specifically investigate the relationship of this enzyme to peptide synthesizing endocrine cells of the anglerfish islet, we performed an immunohistochemical study using several antisera generated against different peptide sequences of the enzyme. PAM antisera labeled cells in the islet organ, pituitary and brain, and fibers in the brain and pituitary gland. The PAM staining pattern in the brain was remarkably similar to the distribution of neuropeptide Y immunoreactivity reported previously. Clusters of cells adjacent to vessels in the anterior pituitary displayed punctate PAM immunoreactivity while varicose fibers were observed in the pituitary stalk and neurohypophysis. Endocrine cells of the islet organ were differentially labeled with different PAM antisera. Comparison of the staining patterns of insulin, glucagon, and anglerfish peptide Y in the islet organ to PAM immunoreactivity suggests a distribution of forms of PAM enzyme in insulin and anglerf ish peptide Y-containing cells, but no overlap with glucagon-producing cells. The results also indicate that PAM immunoreactivity is widely distributed in the brain, pituitary and islet organ of anglerfish in cells that contain peptides that require presence of a C-terminal glycine for amidation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00304521
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  • 96
    Electronic Resource
    Electronic Resource
    The effect of a ventral medial hypothalamic lesion on the insulin-induced hypotensive response in normal rats (1994)
    Springer
    Acta diabetologica 31 (1994), S. 91-97 
    Details
    ISSN: 1432-5233
    Keywords: Insulin ; VMH ; Cardiovascular response ; VMH lesion ; Blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The cardiovascular responses to insulin-induced hypoglycemia were studied in normal and ventral medial hypothalamic (VMH)-lesioned rats. The goal of this study was to investigate the role of the VMH in mediating the insulin-induced decreases in cardiovascular tone. Male Wistar rats were anesthetized with urethane/chloralose. Following the induction of anesthesia, the trachea, femoral artery, and femoral vein were cannulated. The femoral artery was attached to a pressure transducer for cardiovascular monitoring. The cardiovascular activity was recorded using a Modular Instruments Micro 5000 signal processing system. The mean arterial pressure and pulse pressures and heart rate were evaluated. In control studies, a stable plasma glucose and blood pressure were obtained with urethane/chloralose anesthesia for the duration of the experiments. Insulin (2.0 or 5.0 U/kg) significantly decreased the plasma glucose as well as the blood pressure. In VMH-lesioned rats, the lesions were accomplished by radiofrequency, and the cardiovascular response to insulin-induced hypoglycemia was investigated 1 or 6 weeks later. There was no difference in the cardiovascular response to insulin-induced hypoglycemia between the low or high insulin dose after 1 week in VMH-lesioned animals. The low dose after 6 weeks in VMH-lesioned animals did not produce a change in the mean arterial pressure response compared with controls. The pulse pressure was higher than in the sham-lesioned animals, and the plasma glucose response was greater. The high dose after 6 weeks in VMH-lesioned animals in contrast to sham-lesioned animals led to an increased cardiovascular response instead of a decrease. We propose that the decrease in cardiovascular activity in response to insulin-induced hypoglycemia in normal animals can be attributed to a direct or indirect effect on vascular dilation as well as possibly to an inhibition of sympathetic firing. However, it appears that insulin increases the vascular dilation as well as the parasympathetic tone after 1 week in the VMH-lesioned animals, similar to the findings in sham-lesioned animals. However, after 6 weeks, the insulin-induced decreased cardiovascular tone is minimal. Thus, we believe hat the VMH does not have a direct effect in modulating the insulin-induced decrease in cardiovascular tone, but its destruction appears to influence other regulatory centers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00570542
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  • 97
    Electronic Resource
    Electronic Resource
    Immunocytochemical and ultrastructural heterogeneities of normal and glibenclamide stimulated pancreatic beta cells in the rat (1994)
    Springer
    Virchows Archiv 425 (1994), S. 305-313 
    Details
    ISSN: 1432-2307
    Keywords: Rat ; Pancreatic beta cells ; Immunocytochemistry ; Ultrastructure ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract When studied morphologically in semi-thin sections in the rat in vivo, pancreatic beta cells displayed heterogeneous immunoreactivities for insulin and amylin, depending on the islet size and the intra-islet position of the beta cells. In larger islets, cortical beta cells (beta cells with contacts with all islet cell types and with the exocrine parenchyma) which are located in the periphery were more densely immunostained for insulin and amylin than medullary beta cells (beta cells with contacts only with other beta cells) which are located in the centre of the islet. Ultrastructurally, these findings were accompanied by differences in the number of secretory granules and mitochondria. Beta cells in small islets and at extra-islet sites exhibited a dense immunoreactivity. After administration of glibenclamide, immunoreactivities for insulin and amylin were diminished in a time-dependent manner, decreasing first in medullary and thereafter in cortical beta cells of larger islets. Ultrastructurally, the beta cells exhibited the typical signs of stimulation. A minority of beta cells in small islets and all beta cells in extra-islet locations remained unchanged. Thus pancreatic beta cells under basal and stimulatory conditions in vivo exhibit heterogeneity in hormone content and in ultrastructural features. These differences may represent the basis for a functional heterogeneity of the insulin secretory response of the individual beta cell both in vivo and in vitro in states of normal and impaired insulin secretion. As heterogeneity was observed only among beta cells in islets, while single beta cells surrounded by acinar cells exhibited no changes in insulin immunoreactivity, interactions between beta cells as well as between beta cells and other endocrine cells may be critical for expression of heterogeneity within the beta cell population.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00196154
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  • 98
    Electronic Resource
    Electronic Resource
    Structure-activity relationship of covalently dimerized insulin derivatives: correlation of partial agonist efficacy with cross-linkage at lysine B29 (1994)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 350 (1994), S. 213-217 
    Details
    ISSN: 1432-1912
    Keywords: Insulin ; Dimerized insulin derivatives ; Insulin receptor antagonists ; Glucose transport ; 3T3-L1 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of 7 covalently dimerized insulin derivatives on glucose transport in differentiated 3T3-L1 cells were investigated. Symmetric cross-linkage at lysine B29 with a bridge of 2 (oxalyl), 8 (suberoyl) or 12 (dodecanedioyl) carbon atoms produced derivatives with essentially unaltered receptor binding affinity but largely reduced intrinsic activity. Regardless of the chain length, these derivatives inhibited the effect of submaximal insulin concentrations. Insulin derivatives cross-linked at phenylalanine 131 or asymmetrically at 131/1129 were full agonists of the insulin receptor. When lysine B29 was cross-linked with the inactive desoctapeptide(B23-B30)insulin at phenylalanine B1, the intrinsic activity of the resulting dimer was lower than that of insulin, but higher than that of the symmetric B29-dimers. It is concluded that linkage at the B29-lysines, and not at the B1-phenylalanine, leads to partial agonism of dimerized insulin derivatives, regardless of the length of the crosslinker.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00241099
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  • 99
    Electronic Resource
    Electronic Resource
    Insulin and growth in chronic renal failure (1994)
    Springer
    Pediatric nephrology 8 (1994), S. 309-312 
    Details
    ISSN: 1432-198X
    Keywords: Glucose ; Insulin ; Growth ; Chronic renal failure ; Uremia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied glucose metabolism using the hyperglycemic technique in a cross-section of 23 children (15 pubertal, 8 prepubertal) with stable chronic renal failure as a possible cause of their poor growth. Linear growth was expressed as growth velocity standard deviation score (GVSDS). GVSDS correlated with glucose disposal rate but not with insulin sensitivity index in the pubertal (r=0.87,P〈0.001) and prepubertal (r=0.86,P〈0.02) children with chronic renal failure. Thirteen children were followed longitudinally during medical suppression of hyperparathyroidism with dietary phosphate restriction and high-dose phosphate binders. Following significant suppression of serum parathyroid hormone (PTH) levels back to the normal range (932±240 ng/l to 199±50 ng/l), GVSDS, glucose disposal rate and insulin secretion all increased significantly (P〈0.01), with no change in insulin sensitivity index and renal function. The changes in GVSDS correlated with the changes in glucose disposal rate (r=0.86,P〈0.02) and with the changes in insulin secretion (r=0.80,P〈0.01). However, the changes in GVSDS did not correlate with the changes in PTH. The hypothesis that insulin may be more important than PTH in the pathogenesis of growth failure in chronic renal disease deserves further investigation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00866344
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  • 100
    Electronic Resource
    Electronic Resource
    Study on growth hormone and insulin secretion in myotonic dystrophy (1994)
    Springer
    Journal of molecular medicine 72 (1994), S. 508-511 
    Details
    ISSN: 1432-1440
    Keywords: Myotonic dystrophy ; Growth hormone ; Growth hormone releasing hormone ; Insulin ; C-Peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Growth hormone (GH) levels were measured in 12 patients with myotonic dystrophy (MD; 7 men and 5 women, aged 21–49 years) and 14 volunteers after administration of 100 μg GH-releasing hormone (GHRH; 1–29). A 75-g oral glucose tolerance test was carried out to determine glucose, insulin, plasma C-peptide, and urinary C-peptide. The GH level in six MD patients responded normally to GHRH (group I), with a peak of 17.1 ± 1.46 μg/l, compared withcontrols (27.8 ± 19.6 μg/l, NS), and that in the other six patients responded subnormally, with a peak of 3.15 ± 1.46 μg/l, lower than in controls and in group I patients (P 〈 0.001). In group I the insulin response to the glucose tolerance test showed hyperinsulinism and was lower than that in group II patients; stimulated C-peptide was also higher in group II than in group I and in controls; urinary C-peptide levels were parallel to those in previous data. In all MD patients there were a negative correlation between absolute values of GH response to GHRH and insulin response to glucose tolerance test (r = - 0.79, P 〈 0.001). Our data suggest that the failure in GH release and peripheral insulin action is due to a generalized defect in cellular membrane function in MD patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00207479
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