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  • Insulin
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  • 1
    ISSN: 1534-4681
    Keywords: Insulin ; TPN ; Protein kinetics ; Amino acids ; Nutrition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Cancer cachexia is a significant cause of postoperative morbidity and mortality in patients with tumors of the upper gastrointestinal tract. Standard parenteral nutrition (TPN) has failed to alter this. The anabolic effect of insulin has been well documented, and its positive effect on protein economy in cancer patients has been recently demonstrated. This study examines the effect of high-dose insulin and parenteral nutrition on protein kinetics in postoperative cancer patients. Methods: Eleven patients underwent surgery for pancreatic, esophageal, or gastric carcinoma. Postoperatively, patients received standard TPN for 4 days (1 g/kg/day amino acids, 1,000 kcal/day dextrose, 100 g/day lipid), and hyperinsulinemic parenteral nutrition for 4 days (same as standard TPN plus 1.44 U/kg/day regular human insulin) in a crossover design. All patients received both treatments, and the order of treatment was determined randomly. Euglycemia was maintained during insulin infusion via a variable 30% dextrose infusion. Patients underwent protein metabolic studies after each treatment period and rates of whole body and skeletal muscle protein synthesis, breakdown, and net balance were determined by radioisotopic tracer methods using14C-leucine and3H-phenylalanine. Results: Compared with standard TPN (STD), hyperinsulinemic TPN (INS) resulted in a significant increase in skeletal muscle protein synthesis (INS: 52.04±10.22 versus STD: 26.06±6.71 nmol phe/100 g/min, p〈0.05) and net balance of protein (INS: 7.75±4.61 versus STD: −15.10±6.44 nmol phe/100 g/min, p〈0.01), but no difference in skeletal muscle protein breakdown (INS: 44.29±11.54 versus STD: 41.17±5.89 nmol phe/100 g/min). Whole-body net balance of protein also significantly increased with insulin-based TPN, compared with standard TPN (INS: 0.04±0.05 versus STD: −0.08±0.07 µmol leu/kg/min, p〈0.05), but no difference in whole-body protein synthesis (INS: 2.52±0.15 versus STD: 2.49±0.15 µmol leu/kg/min) or whole-body protein breakdown (INS: 2.48±0.16 versus STD: 2.58±0.19 µmol leu/kg/min) was observed. Patients received significantly more calories during the hyperinsulinemic TPN period than during the standard TPN period. There was no difference in total, essential, or branched-chain amino acids, and no difference in serum free fatty acids, triglycerides, or cholesterol was observed between the two treatment periods. Conclusion: High-dose insulin in conjunction with hypercaloric parenteral nutrition causes improved skeletal muscle protein synthesis, skeletal muscle protein net balance, and whole-body protein net balance compared with standard TPN in postoperative cancer patients.
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  • 2
    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.
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  • 3
    ISSN: 1437-9813
    Keywords: Nesidioblastosis ; Insulin ; Radioimmunoassay ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We present two cases of nesidioblastosis, a common cause of persistent hypoglycemia in infancy that, if inadequately treated, can lead to mental retardation. Tissue insulin data obtained from both radioimmunoassay and immunohistochemistry are presented. In each case, the insulin content correlated well with the quantity of insulinpositive cells in each portion of the pancreas. However, the insulin content varied from case to case and from portion to portion of the same pancreas. Thus, discrepancies in clinical results in nesidioblastosis may be due to variability of insulin content in the resected pancreas.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 425 (1994), S. 305-313 
    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.
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  • 5
    ISSN: 1432-0428
    Keywords: Insulin ; islet amyloid polypeptide ; pancreas ; secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To determine whether chronic overproduction of islet amyloid polypeptide alters beta-cell function, we studied a line of transgenic mice which overexpress islet amyloid polypeptide in their beta-cells. At 3 months of age, these transgenic mice had greater pancreatic content of both islet amyloid polypeptide and insulin. Further, basal and glucose-stimulated secretion of both islet amyloid polypeptide and insulin were also elevated in the perfused pancreas of the transgenic animals. These findings demonstrate that chronic overproduction and secretion of islet amyloid polypeptide are associated with increased insulin storage and enhanced secretion of insulin in vitro. This increase in insulin storage and secretion may be due to a direct effect of islet amyloid polypeptide on the beta-cell or a betacell adaptation to islet amyloid polypeptide-induced insulin resistance.
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  • 6
    ISSN: 1432-0428
    Keywords: Insulin ; metformin ; 3-0-methylglucose transport ; non-insulin-dependent diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Metformin has been demonstrated to lower blood glucose in vivo by a mechanism which increases peripheral glucose uptake. Furthermore, the therapeutic concentration of metformin has been estimated to be in the order of 0.01 mmol/l. We investigated the effect of metformin on insulin-stimulated 3-0-methylglucose transport in isolated skeletal muscle obtained from seven patients with non-insulin-dependent diabetes mellitus (NIDDM) and from eight healthy subjects. Whole body insulin-mediated glucose utilization was decreased by 45% (p〈0.05) in the diabetic subjects when studied at 8 mmol/l glucose, compared to the healthy subjects studied at 5 mmol/l glucose. Metformin, at concentrations of 0.1 and 0.01 mmol/l, had no effect on basal or insulin-stimulated (100 ΜU/ml) glucose transport in muscle strips from either of the groups. However, the two control subjects and three patients with NIDDM which displayed a low rate of insulin-mediated glucose utilization (〈20 Μmol·kg−1·min−1), as well as in vitro insulin resistance, demonstrated increased insulin-stimulated glucose transport in the presence of metformin at 0.1 mmol/l (p〈0.05). In conclusion, the concentration of metformin resulting in a potentiating effect on insulin-stimulated glucose transport in insulin-resistant human skeletal muscle is 10-fold higher than the therapeutic concentrations administered to patients with NIDDM. Thus, it is conceivable that the hypoglycaemic effect of metformin in vivo may be due to an accumulation of the drug in the extracellular space of skeletal muscle, or to an effect of the drug distal to the glucose transport step.
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  • 7
    ISSN: 1432-0428
    Keywords: Insulin ; C-peptide ; fructosamine ; triglyceride ; birthweight ; fatty acid ; non-insulin-dependent diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Many ethnic groups at high risk of non-insulin-dependent diabetes mellitus are hyperinsulinaemic by early adult life. This study assessed whether such hyperinsulinaemia is present at birth. Cross sectional comparisons of maternal biochemistry, umbilical cord biochemistry and neonatal anthropometry were made between one ‘low risk’ and three ‘high risk’ ethnic groups, without diabetes in pregnancy in Auckland, New Zealand. The study comprised 123 European, Polynesian (Maori and Pacific Islands) and Indian normal pregnancies. Indian mothers were the smallest, with the highest insulin and non-esterified fatty acid concentrations. Polynesian mothers were the most obese with a higher fructosamine concentration. From these pregnancies, Indian neonates were smaller, slimmer, with the highest cord triglyceride (0.6 mmol/l vs 0.4 mmol/l, p〈0.01), and lowest cord insulin concentrations (7.1 mU/l vs 8.6 mU/l (European), 9.2 mU/l (Polynesian), p〈0.05). Polynesian babies had a high cord insulin: C-peptide ratio (52.5 mU/nmol vs 44.4 mU/ nmol (European), 44.1 mU/nmol (Indian), p=0.05). Although reduced intrauterine growth may contribute to the excess of diabetes and heart disease in Indians, it cannot explain the excess of diabetes in Polynesians. Exposure to minor relative maternal hyperglycaemia in the mother and abnormal neonatal insulin handling (as demonstrated by the higher insulin: C-peptide ratio) may be of long-term significance in Polynesians.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 55 (1994), S. 363-367 
    ISSN: 1432-0827
    Keywords: Skeletal unloading ; Bone formation ; Insulin ; Insulin-like growth factor-I ; Rat femur
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract The alteration of bone metabolism in the femur of rats with skeletal unloading for 4 days was investigated. Skeletal unloading was designed using the model of hindlimb hang in rats. Skeletal unloading caused a significant decrease in femoral weight, calcium, and phosphorus contents in the metaphysis but not diaphysis. Also, the unloading induced a significant decrease of zinc content, alkaline phosphatase activity, and deoxyribonucleic acid (DNA) content in the femoral diaphysis and metaphysis. When the femoraldiaphyseal and metaphyseal tissues from normal and skeletal-unloading rats were cultured in the presence of insulin (10-9 and 10-8 M) for 24 hours in vitro, the hormonal effect to increase alkaline phosphatase activity and DNA content in the diaphysis, but not metaphysis, was lost in the bone tissues from unloading rats. However, the culture with insulin-like growth factor-I (IGF-I; 10-8 and 10-7 M) produced a significant increase of alkaline phosphatase activity and DNA content in both the diaphyseal and metaphyseal tissues from normal and unloading rats. These results demonstrate that skeletal unloading causes an impairment of insulin effect, but not IGF-I effect, on bone metabolism in femoral tissues.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric nephrology 8 (1994), S. 309-312 
    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.
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  • 10
    ISSN: 1432-0738
    Keywords: Key words Cell proliferation ; Pancreas ; 5-Bromo-2′-deoxyuridine (BrdU) ; Immunohistochemistry ; Hormones ; Insulin ; Glucagon ; Somatostatin ; Phenobarbitone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A previous study demonstrated that administration of phenobarbitone to male AP Wistar rats for up to 7 days caused alterations in labelling indices (LIs) in several different tissues (including a reduction of the endocrine pancreas population LI) as determined by immunohistochemical visualisation of 5-bromo-2′-deoxyuridine (BrdU) incorporation into S-phase nuclei. The primary objective of this study was to determine whether treatment with phenobarbitone influenced the replicative states of specific cohorts of the islet (of Langerhans) cell population or generated a uniform depression of LI. Quantitation of the LIs of individual islet cell cohorts was achieved by utilisation of a dual immunohistochemical staining method for BrdU and islet hormones (insulin, glucagon and somatostatin) using a sequential peroxidase anti-peroxidase (PAP)/alkaline phosphatase anti-alkaline phosphatase (APAAP) method employing diaminobenzidine and New Fuchsin chromogens, respectively. We observed reductions, increases and no change in LIs of insulin-, glucagon- and somatostatin-positive cells, respectively. We conclude that the decreased LI of the insulin-positive cohort was not countered entirely by the LI increase in the glucagon-positive cohort due to the larger size of the former. Furthermore, the effects of phenobarbitone treatment are not manifested generally in the islet cell population but in the insulin- and glucagon-positive cohorts only. The causation of these effects is unknown but is likely to be due to enhanced carbohydrate and hormone metabolism. We believe that the visualisation and quantitation of replicating cells in specific hormone-positive cohorts of the islet cell population provide opportunities for understanding the influence of xenobiotics and disease processes on pancreatic function.
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 153 (1994), S. 409-410 
    ISSN: 1432-1076
    Keywords: Key words     Children ; Diabetes ; Insulin ; Jet injection ; Pain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract      The aim of this study was to investigate whether insulin application by jet injector is less painful than by needle. Pain was scored by 41 diabetic and seven healthy volunteers after injections with both methods. Injections by jet were no less painful than those by needle but produced several local side-effects.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    European biophysics journal 23 (1994), S. 177-187 
    ISSN: 1432-1017
    Keywords: Molecular dynamics simulation ; Insulin ; Crosslinked insulin ; Single chain insulin ; Active conformation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract Molecular dynamics simulations were carried out on an insulin crosslinked between the N-terminal A chain and the C-terminal B chain to form a so-called mini-proinsulin: N α -A1-N ε -B29-diaminosuberoyl insulin (DASI). To investigate the influence of crosslinking on the dynamics of the insulin moiety, the bridge was removed from a transient DASI structure and simulation was carried on independently with the then unlinked (ULKI) as well as with the crosslinked species. The effects of crystal packing and quaternary interactions were checked by simulating both types of monomers and dimers known from the hexamer structure. All simulations were compared to previous ones of native insulin. DASI shows general similarity to the native simulations in most parts of the structure. Deviations are visible in the segments to which the bridge is directly connected, i.e. their flexibility is reduced. Upon removal of the bridge the ULKI simulations reapproach those of native insulin. The influence of the bridge spreads over the whole molecule, but all of its main structural features remain intact. The simulations suggest that the displacement of the C-terminal B chain of native insulin, considered important for receptor interaction, is prevented by the bridge, which also partially shields some binding residues. This is in accordance with the poor biological potency of A1-B29-crosslinked insulins.
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  • 13
    ISSN: 1432-2013
    Keywords: Glucose oxidation ; Glucose infusion ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To determine the limits to oxidation of exogenous glucose by skeletal muscle, the effects of euglycaemia (plasma glucose 5 mM, ET) and hyperglycaemia (plasma glucose 10 mM, HT) on fuel substrate kinetics were evaluated in 12 trained subjects cycling at 70% of maximal oxygen uptake (VO2, max) for 2 h. During exercise, subjects ingested water labelled with traces of U-14C-glucose so that the rates of plasma glucose oxidation (R ox) could be determined from plasma 14C-glucose and expired 14CO2 radioactivities, and respiratory gas exchange. Simultaneously, 2-3H-glucose was infused at a constant rate to estimate rates of endogenous glucose turnover (R a), while unlabelled glucose (25% dextrose) was infused to maintain plasma glucose concentration at either 5 or 10 mM. During ET, endogenous liver glucose R a (total R a minus the rate of infusion) declined from 22.4±4.9 to 6.5±1.4 μmol/min per kg fat-free mass [FFM] (P〈0.05) and during HT it was completely suppressed. In contrast, R ox increased to 152±21 and 61±10 μmol/min per kg FFM at the end of HT and ET respectively (P〈0.05). HT (i. e., plasma glucose 10 mM) and hyperinsulinaemia (24.5±0.9 μU/ml) also increased total carbohydrate oxidation from 203±7 (ET) to 310±3 μmol/min per kg FFM (P〈0.0001) and suppressed fat oxidation from 51±3 (ET) to 18±2 μmol/min per kg FFM (P〈0.0001). As the rates of oxidation at more physiological euglycaemic concentrations of glucose were limited to 92±9 μmol/ min per kg FFM, and were similar to those reported when carbohydrate is ingested, the results of the current study suggest that the concentrations of glucose and insulin normally present during prolonged, intense exercise may limit the rate of muscle glucose uptake and oxidation.
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  • 14
    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.
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  • 15
    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.
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  • 16
    ISSN: 1439-6327
    Keywords: Catecholamines ; Insulin ; Growth hormone ; ACTH ; Erythropoietin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To establish whether or not hypoxia influences the training-induced adaptation of hormonal responses to exercise, 21 healthy, untrained subjects [26 (2) years, mean (SE)] were studied in three groups before and after 5 weeks' training (cycle ergometer, 45 min· day−1, 5 days· week−1). Group 1 trained at sea level at 70% maximal oxygen uptake ( $$\dot V$$ O2max), group 2 in a hypobaric chamber at a simulated altitude of 2500 m at 70% of altitude $$\dot V$$ O2max, and group 3 at a simulated altitude of 2500 m at the same absolute work rate as group 1. Arterial blood was sampled before, during and at the end of exhaustive cycling at sea level (85% of pretraining of $$\dot V$$ O2max). $$\dot V$$ O2 increased by 12 (2)% with no significant difference between groups, whereas endurance improved most in group 1 (P 〈 0.05). Training-induced changes in response to exercise of noradrenaline, adrenaline, growth hormone, β-endorphin, glucagon, and insulin were similar in the three groups. Concentrations of erythropoietin and 2,3-diphosphoglycerate at rest did not change over the training period. In conclusion, within 5 weeks of training, no further adaptation of hormonal exercise responses takes place if intensity is increased above 70% $$\dot V$$ O2max. Furthermore, hypoxia per se does not add to the training-induced hormonal responses to exercise.
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  • 17
    ISSN: 1573-6903
    Keywords: Insulin ; chick embryo ; retina ; development ; HPLC analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Retinas of chick embryos contain insulin (1) and further, are capable of synthesizing it, as demonstrated by incubating retinas at different ages (7th–18th day) with [3H]leucine. The synthesized radioactive insulin was isolated and assayed by means of a HPLC procedure. The synthesis of insulin was found to be highest in the youngest retinas studied (day 7), afterwards it declined with age except for an increment found at 14–15 day. Explants of chick embryo retinas, cultured in vitro, rapidly degraded insulin. Nevertheless, the content of immunoreactive insulin in retinal explants diminished slowly with the age of culture, so that, after 8 days of incubation, it was about 60% of the content found in the retinas at the beginning of incubation. This was proof that cultured explants are capable of efficiently synthesizing insulin. The synthesized [3H]insulin was released from explants into the medium. This was evident also after 6–8 days in culture.
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  • 18
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Molecular Reproduction and Development 37 (1994), S. 398-406 
    ISSN: 1040-452X
    Keywords: Preimplantation embryo ; Insulin ; IGFs ; Protein synthesis ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: Previously constructed protein databases for two stages of preimplantation mouse embryogenesis, the compacted eight-cell stage and the fully expanded blastocyst stage, have been used to analyze the effects of insulin, IGF-I, and IGF-II on protein synthesis in these developmental stages. Proteins were labeled by placing, for 2 hr, synchronous cohorts of 35-50 embryos into human tubal fluid (HTF) medium containing L-[35S]-methionine (1 mCi/ml) in the presence or absence of one of the growth factors. The embryos were then washed with medium and lysed. Samples were processed for 2-D gel analysis. For each embryonic stage and each growth factor, four or five experimental replicates were done and the gel images were compared using the PDQUEST system. Using the computer-assisted analysis, we were able to identify proteins that showed a statistically significant (P 〈 0.05) change in synthesis. At the eight-cell stage of development insulin caused increased synthesis of two proteins and decreased synthesis in three proteins. Insulin-treated blastocyst stage embryos exhibited an increased synthesis in eight proteins and decreased synthesis for one protein. The effect of IGF-I at the eight-cell stage of development was mostly inhibitory; the synthesis of only one protein increased and the synthesis of five proteins showed a decrease. Similar results were obtained with blastocyst stage embryos; four proteins demonstrated an increase in synthesis while 14 proteins showed a decrease. Eight-cell stage embryos incubated with IGF-II had seven proteins with a decreased synthesis, although in blastocyst stage embryos, nine proteins showed increased synthesis. However, seven IGF response proteins were found to be proteins that showed significant changes in isotope incorporation during the eight-cell to blastocyst stage of development (Shi et al., 1993). In all, 54 proteins were affected, and these were unique; thus, protein synthesis in preimplantation mouse embryos is influenced by insulin and the IGFs, and further, each growth factor affects specific proteins. © 1994 Wiley-Liss, Inc.
    Additional Material: 8 Ill.
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  • 19
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Microscopy Research and Technique 27 (1994), S. 61-70 
    ISSN: 1059-910X
    Keywords: Salivary gland ; Diabetes ; Insulin ; Electron microscopy ; Streptozotocin ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Natural Sciences in General
    Notes: Effects of experimental diabetes on rat submandibular glands have been documented, but earlier reports suggested that diabetes caused an extensive cellular degeneration and a replacement of the parenchymal cells by fibrous connective tissue. Such observations, however, are difficult to reconcile with the relatively normal physiological responsiveness of the gland (Anderson and Suleiman, 1989). This study, therefore, reexamined the histological, histochemical and ultrastructural effects of streptozotocin-induced diabetes on rat submandibular glands. The tissues were examined at 3 weeks, and 3 and 6 months after the induction of diabetes, and compared with glands from age-matched controls by both light and electron microscopy. Light microscopically, the proportional volumes of the acini and granular ducts remained constant in control rats at about 48% and 38% respectively. In diabetic animals the volume density of the acini increased progressively to 62%, whereas that of the granular ducts decreased to 20%. The diameter and number of granular ducts were reduced in diabetic animals, but acinar cell profile area was only affected 6 months after the induction of diabetes. Ultrastructurally, there was an accumulation of lipid in the acinar cells and, with increasing duration of diabetes, the number of autophagic structures in both the acini and the granular ducts increased. Although there was evidence of some cellular degeneration it was never excessive. Morphometry showed that the volume density of secretory granules within the acinar cells was unaffected, but there was a significant reduction in the volume density of secretory granules within the granular ducts. Thus, in the rat submandibular gland the greatest effect of streptozotocin-induced diabetes was to cause hypotrophic changes in the cells of the granular ducts. The relative contributions of a direct effect of insulin insufficiency and the hypogonadal effects of diabetes, however, are not known. © 1994 Wiley-Liss, Inc.
    Additional Material: 8 Ill.
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  • 20
    ISSN: 1432-1440
    Keywords: Diabetes mellitus ; Enteral formula ; Fructose ; Insulin ; Xylitol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To verify the benofit of nonglucose carbohydrates and fiber in enteral formula diets we studied the postprandial metabolism of eight healthy subjects after the intake of two helpings (25 g carbohydrates each) of five commonly used enteral formulas over 4 h. There were no significant differences in postprandial concentrations of blood glucose among the formulas. The area under the curve of postprandial insulin values, however, was significantly smaller after consumption of the fructose-containing formula (1948±285 μU min ml−1, P〈0.05) than after fiber-free (3222 ±678 μU min ml−1) or two fiber-containing products (2664±326 μU min ml−1, P〈0.05; and 3040±708 μU min ml−1, P〈0.05). The insulin area of the xylitol-containing formula (2307±364 μU min ml−1) was significantly smaller compared to the fiber-free product (P〈0.05). In addition, we found the postprandial increase in triglycerides to be significantly higher after the xylitol-containing formula (from 0.93±0.14 to 1.25±0.22 mmol/1) than after the fiber-free product (from 0.82±0.13 to 0.97±0.16 mmol/1, P〈0.05) or the two fiber-containing products (from 0.88±0.16 to 0.96±0.18 mmol/1, P〈0.05; and from 0.80±0.08 to 0.95±0.10 mmol/l, P〈0.05). We conclude that a patient with type 11 diabetes may benefit from replacing glucose and glucose-equivalent carbohydrates with fructose or xylitol.
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  • 21
    ISSN: 1432-1440
    Keywords: Angiotensin II ; Insulin ; Smooth muscle cell ; Vascular
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hypertension has a high prevalence among subjects with decreased insulin sensitivity and/or hyperinsulinemia. Furthermore, angiotensin II plays a pivotal role in the regulation of vascular tone and is known to induce hypertrophy and/or hyperplasia in vascular smooth muscle cells. In the present study, the effect of insulin on angiotensin II induced smooth muscle cell growth (Wistar-Kyoto rat) was investigated. Cell growth was assessed by the measurement of [3H]thymidine incorporation into cell DNA. Insulin in a concentration range of 1.7 × 10−10–1.7 × 10−6 M lacked any effect on cell DNA synthesis. However, insulin enhanced the angiotensin 11 induced DNA synthesis in a concentration-dependent manner. This effect was similar in cells with a weak and in cells with a marked response in DNA synthesis to stimulation with 100 nM angiotensin 11. In conclusion, insulin is able to enhance angiotensin 11 induced DNA synthesis and may therefore function as a growth cofactor in vascular smooth muscle cells.
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  • 22
    ISSN: 1432-1440
    Keywords: Acromegaly ; Blood glucose ; Bromocriptine ; Glucose tolerance test ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It is not known whether the beneficial effect of bromocriptine on glucose homeostasis in acromegaly is limited by a certain duration of therapy. To elucidate this problem, oral glucose tolerance tests were performed in 12 acromegaly patients before bromocriptine medication, under therapy (15.0 ± 6.8 mg/day for 12 ± 3 years), and during a 2-week drug withdrawal after long-term treatment. Initially altered glucose tolerance was normalized in 4 of 5 patients under bromocriptine therapy. During drug withdrawal the mean fasting glucose level and the mean glucose concentration at 120 min after oral glucose load increased from 5.05 ± 0.61 to 5.77 ± 0.78 mmol/1 and from 5.61 ±2.05 to 7.55 ± 3.05 mmol/1, respectively. A deterioration in glucose homeostasis was observed in 9 patients, and impaired glucose tolerance was ameliorated (but not to normal range) in 2 when bromocriptine was withdrawn. The proportion of alterations in glucose tolerance during drug withdrawal corresponded to that before the beginning of long-term bromocriptine treatment. Impaired glucose tolerance, observed in 2 patients under bromocriptine treatment, seemed to be compensated because a distinct elevation of glycosylated hemoglobin A1c was not observed. Bromocriptine led to a significant decrease in basal as well as glucose-stimulated insulin levels, and growth hormone secretion during oral glucose load was reduced in all 12 patients. Similarly to the increased growth hormone secretion after drug withdrawal in 11 patients, a rise in glucose-stimulated insulin secretion was found in all patients; hereby, the mean insulin levels at 0 and 120 min during oral glucose load rose significantly from 7.5 ± 2.6 to 12.1 ± 5.1 mU/1 (P〈0.01) and from 71.3±52.1 to 101.4±50.7 mU/1 (P〈0.02), respectively. A direct relationship between disturbance in glucose homeostasis and degree of hypersomatotropism was not observed. Our data confirm that the beneficial effect of bromocriptine therapy on glucose homeostasis in selected patients with acromegaly is still present after dopaminergic treatment over a mean period of 12 years. Compared with the published rates on improved glucose homeostasis under octreotide, the effect of bromocriptine seems to be more favorable.
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  • 23
    ISSN: 1432-0827
    Keywords: Insulin ; Cartilage ; Growth ; Condyle ; Mandible ; Mouse ; In vitro
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Condylar cartilages were cultured in the form of organ cultures on top of collagen sponges in medium containing 2% fetal calf serum and were treated with 3.5–350 nM insulin for 6 days. Doses of 175 nM of insulin caused a marked increase (+96%) in DNA synthesis and in proteoglycan production (+74%), features that manifested themselves structurally by a 60% increase in overall size of the cultured explants. Using a tissue culture system comprised of cartilage progenitor cells, insulin was found to enhance the differentiation of the progenitor cells so that by 6 days in culture and appreciable nodule of differentiated chondrocytes developed. The latter was surrounded by perichondrial cells whereas the extracellular matrix within the newly formed, insulin-induced, nodule reacted positively for cartilagespecific antigens (type II collagen and bone sialoprotein). It is suggested that insulin induces a direct stimulatory effect on progenitor cell proliferation, cartilage differentiation, and extracellular matrix deposition.
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  • 24
    ISSN: 1437-9813
    Keywords: Parenteral hyperalimentation ; Insulin ; Adrenergic alpha-receptor blockers ; adrenergic beta-receptor blockers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hyperglycemia and relative hypoinsulinemia are characteristic in the post-traumatic period. The altered insulin kinetics in this phase are dependent on many factors, which include stimulation of adrenoreceptors of pancreatic beta-cells and increased urinary clearance of insulin. Using the young rabbit as an experimental model, two series of experiments were designed. In study 1 (effect of trauma on serum insulin/glucose [I/G] ratio and urinary loss of insulin) two groups of animals (control and trauma) on parenteral nutrition were studied during 4 days. In study 2, in an acute 3-h period the effects of alpha- and beta-adrenoceptor blockers on insulin secretion were investigated. The animals were divided into four groups: control, trauma, trauma + phentolamine, and trauma + propranolol. In study 1 it was demonstrated that after trauma there was a decrease in I/G ratio and an increase in urinary loss of insulin, but no alteration in absolute levels of serum insulin. In study 2 we could demonstrate that treatment with adrenoceptor blockers did not prevent the lowering effect of trauma on I/G ratio. It is suggested that the diabetes-like state of the post-injury period is a complex phenomenon that is dependent on other important factors, as well as catecholamine inhibition of insulin secretion.
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  • 25
    ISSN: 1432-0568
    Keywords: Fetal antigen 1 ; Insulin ; Pancreas ; Development ; Exocrine ; Endocrine ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Monospecific rabbit anti-human fetal antigen 1 (FA1), was used to examine the distribution of FA1 during the development of the human fetal pancreas and liver using an indirect immunoperoxidase technique. FA1 was expressed by 94% of the glandular epithelial cells of the branching ducts in the pancreatic anlage at week 7 of gestation. This pattern changed during the development of the human pancreas, 64% of the glandular cells being FA1 positive at week 17 of gestation, decreasing to 11% in the infant (4 months after birth). In the infant and adults the FA1 expression was restricted to a subpopulation of β-cells within the islets of Langerhans. Insulin immunoreactive cells were scattered throughout the epithelium of primitive branching pancreatic ducts at week 7 of gestation, well before the formation of islets. From the 7th through to the 17th week of gestation, FA1 was found in the cytoplasm of fetal hepatocytes, whereas no staining was observed in the liver from a 4-month-old infant. No FA1 expression was found in the epithelium of the developing gut. The present findings indicate that the glandular epithelial cells in the developing pancreas may serve as stem cells, which, if appropriately induced, may differentiate into endocrine cells. Fetal antigen 1 (FA1) may take part in or be a result of this differentiation.
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  • 26
    ISSN: 1432-0428
    Keywords: Insulin ; HDL ; cholesterol ; atherosclerosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Both Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic individuals are at increased risk of developing ischaemic heart disease. Insulin excess, present in both diabetic groups, may play an important pathophysiologic role in accelerating the atherogenic process. In this study, cultured human skin fibroblasts were incubated with varying concentrations of insulin to test the role of insulin on cell cholesterol homeostasis and on HDL3-mediated removal of excess cholesterol from cells. Insulin excess (1-2-100 nmol/l) resulted in a significant dose-dependent reduction in HDL3-mediated cholesterol efflux from the intracellular unesterified cholesterol pool of cultured human skin fibroblasts. Similar insulin concentrations resulted in impaired HDL-mediated cholesterol efflux from the cell membrane but had no effect on non-HDL-mediated efflux. The effect of insulin on cholesterol esterification and biosynthesis was assessed by14C-oleate labelling. The addition of HDL3 (50 μg) resulted in a significant decrease in14C-labelled cholesterol ester, reflecting a decrease in intracellular unesterified cholesterol, which was partially reversed by the addition of insulin. Insulin had no effect on the incorporation of14C-oleate into unesterified cholesterol. During simultaneous incubation of fibroblasts with LDL and HDL, insulin resulted in an increase in cholesterol esterification and inhibited ability of HDL to promote the decrease in esterification. Thus, we have shown that insulin exess counteracts the beneficial effects of HDL that involve removal of cellular cholesterol and may in part promote atherogenesis by this mechanism
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  • 27
    ISSN: 1432-0428
    Keywords: Insulin ; calcium ; magnesium ; pH ; nuclear magnetic resonance spectroscopy ; erythrocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Elevated erythrocyte cytosolic free calcium, and suppressed free magnesium and pH values are associated with the hyperinsulinaemia and insulin resistance of hypertension, obesity, and Type 2 (non-insulin-dependent) diabetes mellitus. To determine the role of insulin in this process, we utilized 19F- and 31P-nuclear magnetic resonance spectroscopy to study the cellular ionic effects of insulin in vitro on normal human erythrocytes. Insulin elevated cytosolic free calcium levels in a dose- and time-dependent manner. The effect began at 10 μU/ml, peaked at 200 μU/ml, and continued at both the 500 μU/ml and 1000 μU/ml doses. At 200 μU/ml, free calcium levels rose from 24.6±2.5 nmol/l to a peak value at 120 min of 66.4±11 nmol/l (p〈0.05 vs basal), levels remaining elevated throughout the incubation (45.7±5.6 nmol/l at 60 min, and 47.9±9.1 nmol/l at 180 min, p〈0.05 vs basal, respectively). Similarly, insulin also increased intracellular free magnesium at all time points (basal: 177± 11 μmol/l; 60 min: 209±19 μmol/l; 120 min: 206±22 μmol/l; and 180 min: 202±12 μmol/l; p〈0.05 vs basal at all times). No insulin-induced changes in pH were observed. We conclude (i) that insulin in physiological concentrations may participate in regulating divalent cations in the mature human erythrocyte, (ii) that insulin per se cannot account for the previously described cellular ionic lesions of hypertension and diabetes, and (iii) that future clinical studies of cell ion metabolism should be conducted in the fasting state, be controlled for ambient circulating insulin levels, or both.
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  • 28
    ISSN: 1432-2013
    Keywords: K+-channel ; Ca2+ ; Apamin ; Pancreas ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The whole-cell configuration of the patchclamp technique was used to characterize the biophysical and pharmacological properties of an oscillating K+-current that can be induced by intracellular application of GTP[γS] in mouse pancreatic B cells (Ämmälä et al. 1991). These K+ conductance changes are evoked by periodic increases in the cytoplasmic Ca2+ concentration ([Ca2+]i) and transiently repolarize the B cell, thus inhibiting action-potential firing and giving rise to a bursting pattern. GTP[γS]-evoked oscillations in K+ conductance were reversibly suppressed by a high (300 μM) concentration of carbamylcholine. By contrast, α2-adrenoreceptor stimulation by 20 μM clonidine did not interfere with the oscillatory behaviour but evoked a small sustained outward current. At 0 mV membrane potential, the oscillating K+-current elicited by GTP[γS] was highly sensitive to extracellular tetraethylammonium (TEA; 70% block by 1 mM). The TEA-resistant component, which carried approximately 80% of the current at −40 mV, was affected neither by apamin (1 μM) nor by tolbutamide (500 μM). The current evoked by internal GTP[γS] was highly selective for K+, as demonstrated by a 51-mV change in the reversal potential for a sevenfold change in [K+]o. Stationary fluctuation analysis indicated a unitary conductance of 0.5 pS when measured with symmetric (≈ 140mM) KCl solutions. The estimated singlechannel conductance with physiological ionic gradients is 0.1 pS. The results indicate the existence of a novel Ca2+-gated K+ conductance in pancreatic B cells. Activation of this K+ current may contribute to the generation of the oscillatory electrical activity characterizing the B cell at intermediate glucose concentrations.
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  • 29
    ISSN: 1573-4935
    Keywords: Insulin ; L6 myoblast ; protein synthesis ; protein kinase C ; arachidonate ; DAG
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Insulin stimulated protein synthesis in L6 myoblasts but did not increase the labelling of DAG or the release of phosphocholine from phosphatidylcholine. The DAG lipase inhibitor, RHC 80267, more than doubled the amount of label appearing in DAG but did not stimulate protein synthesis. Even in the presence of the DAG lipase inhibitor insulin failed to have any effect on DAG labelling, and conversely RHC 80267 did not modify the insulin-induced increase in protein synthesis. These results suggest that endogenous DAG production is not involved in the stimulation of protein synthesis by insulin. However, exogenous diacylglycerols (1-oleoyl-2-acetyl glycerol and 1-stearoyl-2-arachidonoyl glycerol) both stimulated protein synthesis in L6 myoblasts. The efficacy of the former (arachidonatefree) DAG suggested that their action was by activation of protein kinase C rather than by arachidonate release and prostaglandin formation. Ibuprofen, an inhibitor of cyclo-oxygenase failed to block the effects of insulin whereas a second cyclo-oxygenase inhibitor, indomethacin had only a partial inhibitory effect. The protein kinase C (PKC) inhibitor, RO-31-8220, totally blocked the effect of insulin. Since indomethacin is also recognised to inhibit phospholipase A2, the data suggests that insulin acts on protein synthesis in myoblasts by arachidonate activation of PKC.
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  • 30
    Electronic Resource
    Electronic Resource
    Springer
    Journal of fluorescence 3 (1993), S. 215-217 
    ISSN: 1573-4994
    Keywords: Insulin ; lecithin liposomes ; light scattering ; fluorescence anisotropy ; 1,6-diphenyl-1,3,5-hexatriene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The interaction between zinc-stabilized insulin and lecithin liposomal membranes was studied using DPH fluorescence anisotropy and light-scattering techniques. To ascertain a possible influence of a charge on the insulin molecule, experiments were performed at pH 4.5 (insulin possesses a positive charge) and at pH 7.4 (the charge of insulin is negative). Measurements at pH 4.5 revealed significant changes in scattered light intensity induced by the addition of insulin to lecithin liposomes. With increasing time of storage of liposomes the insulin effect became faster and more pronounced. At pH 7.4, significant changes in scattered light were registered only in the case of liposomes stored for 5 days. In these liposomes a peroxidation process of lecithin was revealed. No significant changes induced by insulin were observed in DPH fluorescence anisotropy either at pH 4.5 or at pH 7.4, which suggested the absence of an interaction of insulin with the hycrophobic core of liposomes. Thus, the observed changes in scattered light could be interpreted in terms of the insulin association to the liposomal surface in the case of phospholipid peroxidation and/or acidic pH.
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  • 31
    Electronic Resource
    Electronic Resource
    Springer
    The journal of membrane biology 135 (1993), S. 1-10 
    ISSN: 1432-1424
    Keywords: Glucose transporter ; GLUT ; GLUT isoforms ; Oxidative phosphorylation ; Insulin ; Transporter activation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
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  • 32
    ISSN: 1432-1424
    Keywords: Insulin ; Immuno-electron microscopy ; Caveolae ; Na+/K+-ATPase ; Glucose transporters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract We have quantitated and studied the topology of isoforms of the Na+/K+-ATPase and of the glucose transporter in rat adipocyte plasma membranes. Adipocytes were incubated with or without insulin for 15 min. Sheets of native plasma membrane, with the cytoplasmic face exposed, were prepared by adsorption to EM grids. Grids were incubated in parallel with monoclonal antibodies against the Na+/ K+-ATPase isoforms α1 and α2, and the glucose transporter isoforms GLUT1 and GLUT4, followed by immunogold labeling, negative staining and quantitation by counting of the gold particles in electron micrographs. In addition, the distribution of glucose transporters and Na+/K+-ATPase isoforms in subcellular membrane fractions prepared by an established fractionation procedure was monitored by Western blotting. We found that the Na+/K+-ATPases and the glucose transporters were confined to the planar part of the plasma membrane, without association to caveolar invaginations. The vast majority of the Na+/K+-ATPase molecules in the adipocyte plasma membrane were of the α2 isoform; GLUT4 was the dominating glucose transporter isoform. The total number of Na+/K+-ATPase molecules labeled in the plasma membrane was 3.5×105 per cell, independent of insulin stimulation. Concomitantly, insulin increased GLUT4 labeling sevenfold to a value of 3.5×105 per cell.
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  • 33
    ISSN: 1432-5233
    Keywords: Diabetes mellitus ; Immunocytochemistry ; In situ hybridization ; Insulin ; Streptozotocin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The relative efficacy of immunocytochemistry versus in situ hybridization in identifying residual beta cells was studied in rats with streptozotocin-induced diabetes. Consecutive sections of pancreas of streptozotocin-treated diabetic rats and control animals were alternately subjected to in situ hybridization (synthetic oligonucleotides complementary to rat preproinsulin mRNA) and immunocytochemistry (monoclonal antibodies to insulin). The results obtained with both methods were quantitated with the use of computer-assisted image analysis, and the ratio of cells positive by immunocytochemistry to those positive by in situ hybridization was determined. Under normoglycaemic conditions the values obtained by immunocytochemistry correlated well with those obtained by in situ hybridization (immuno/in situ 〉 95%). In the streptozotocin diabetic animals, however, immunocytochemistry resulted in a distinct underestimation of the number of residual beta cells (immuno/in situ 〈 80%). This difference was even more striking in small islet cell clusters (〈100 μm) immuno/in situ 20%). These results suggest that in situ hybridization for prohormone mRNA is the method of choice for the identification of residual or regenerating beta cells with very low insulin content. Caution should be used when interpreting quantitative data in diabetic conditions that are based exclusively on immunocytochemical detection methods.
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  • 34
    ISSN: 1432-5233
    Keywords: C-peptide ; Diabetes mellitus ; Glucose clamp ; Insulin ; Proinsulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Elevated fasting proinsulin immunoreactive material (PIM) has previously been found in patients with type 2 (non-insulin-dependent) diabetes mellitus. It is not known whether this is a genetic trait or whether it is related to the manifestation of type 2 diabetes. Neither is it clear whether the raised fasting insulin immunoreactivity previously observed in first-degree relatives of patients with type 2 diabetes is due to raised PIM. Furthermore, it has not been investigated whether first-degree relatives have altered PIM responses to different secretagogoues. To study this, PIM, insulin and C-peptide were measured in patients with type 2 diabetes, in their first-degree relatives and in healthy control subjects in the fasting state and in relatives and controls during a hyperglycemic clamp. At the end of the hyperglycemic clamp, 0.5 mg of glucagon was given intravenously to stress the beta cells further. Fasting PIM concentrations were significantly higher in patients with type 2 diabetes (P〈0.05). These patients did not have significantly elevated fasting insulin levels when corrected for PIM. In the relatives, fasting insulin concentrations were elevated but PIM levels were normal suggesting that the increase in fasting insulin concentrations reflected an increase in true insulin. The incremental PIM, insulin and C-peptide responses to glucose and glucagon in the relatives were not different from those in the controls. We conclude that elevated fasting PIM levels in patients with type 2 diabetes seem not to be a genetic trait. First-degree relatives of patients with type 2 diabetes are truly hyperinsulinemic in the fasting state, and they have proportional PIM, insulin and C-peptide responses to glucose and glucagon.
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  • 35
    ISSN: 1432-5233
    Keywords: Cyclic AMP antagonist ; Inositol phosphates ; Insulin ; Noradrenaline ; Prostaglandin E
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This report shows that the cyclic AMP antagonist cyclic PIP is present in all organs and tissues of the rat so far examined: brain, heart, lung, intestine, kidney, liver, spleen, skeletal muscle and fat. The synthesis of cyclic PIP is stimulated by insulin or noradrenaline (α-adrenergic action) in a dose-dependent fashion. Increasing cyclic PIP synthesis with increasing insulin concentrations matches the insulin receptor binding curves. Cyclic PIP levels in blood serum remain low after hormonal stimulation and no cyclic PIP can be detected in urine. As an indication of its ubiquity, cyclic PIP was even detected in yeast. Prostaglandin E (as shown by incorporation of [3H]PGE into cyclic PIP and demonstration of a constant specific activity), myo-inositol (as shown by acid hydrolysis of the dephosphorylated cyclic PIP and mass spectrometric identification of the products) and one phosphate (as shown by the ionic nature of cyclic PIP and its inactivation by phosphodiesterase plus phosphatase) are components of cyclic PIP. Chemical derivatization experiments of cyclic PIP suggest the phosphate to be bound to myo-inositol and the myo-inositol phosphate to the prostaglandin E by its C15-hydroxyl group.
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  • 36
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    Aesthetic plastic surgery 17 (1993), S. 113-115 
    ISSN: 1432-5241
    Keywords: Autologous adipose tissue ; Techniques ; Insulin ; Centrifugation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Different techniques for processing adipose tissue were tested in 40 Swiss Albino female mice. Our study established that the use of insulin did not show any positive effect on survival of adipocytes during their transplantation. Likewise, the use of a centrifuge machine, at high or low speed, for separating the adipose tissue components, completely destroyed the adipose cells and did not allow their survival.
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  • 37
    ISSN: 1432-0878
    Keywords: IAPP (islet amyloid polypeptide) ; Endocrine pancreas ; In situ hybridization ; Immunocytochemistry ; Somatostatin ; Insulin ; Rat (Sprague Dawley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The expression of the islet amyloid polypeptide (IAPP) gene within the endocrine pancreas and its correlation with insular neuroendocrine peptide localization were investigated in the rat. In situ hybridization with a 35S-labelled IAPP-mRNA specific oligonucleotide probe was combined with immunocytochemistry. In situ hybridization alone showed strong autoradiographic labelling of the pancreatic islets. In situ hybridization combined with immunocytochemistry for IAPP, revealed labelling of the IAPP-immunoreactive cells. However, when in situ hybridization was combined with immunocytochemistry for proinsulin, we noted a lack of proinsulin immunoreactivity in some peripherally located autoradiographically labelled islet cells. Furthermore, combination of in situ hybridization and immunocytochemistry for somatostatin showed autoradiographic labelling of somatostatin cells to a varying degree. This was further confirmed by showing cellular co-localization of IAPP and somatostatin by immunocytochemical double staining. We conclude that IAPP is mainly synthesized in insulin cells. Additionally, a subpopulation of the somatostatin cells is capable of IAPP synthesis. This may account for the relatively small reduction in the content of IAPP-mRNA in islets compared to the marked reduction of insulin mRNA after streptozotocin-induced diabetes in rats as previously reported.
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  • 38
    ISSN: 1432-0878
    Keywords: Endocrine pancreas ; IGF-1 ; IGF-2 ; Insulin ; Glucagon ; Somatostatin ; Pancreatic polypeptide ; Man ; Dog ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Immunohistochemical techniques were used to study the occurrence and distribution of insulin-like growth factor 1 (IGF-1) and IGF-2 in the pancreas of man, dog, and rat and their possible coexistence with insulin (INS), glucagon (GLUC), somatostatin (SOM) and pancreatic polypeptide (PP). All control experiments, including pre-absorption of the antisera with synthetic peptide hormones, indicated the specificity of the immunoreactions obtained. In all species investigated, IGF-2-immunoreactivity occurred exclusively in INS-immunoreactive cells as was found by the use of consecutive sections and double immunofluorescence on identical sections. In contrast, IGF-1-immunoreactivity co-existed with GLUC-immunoreactivity. In man, singular SOM-immunoreactive cells also contained IGF-1-immunoreactivity. Thus, IGF-1 and IGF-2 can be localized by means of immunohistochemistry in the mammalian pancreas, and can be shown to occur in different islet cell populations. It is presumed that IGF-1 derived from A-cells and/or D-cells acts on the B-cells in a paracrine manner. The co-existence of IGF-2-immunoreactivity and INS-immunoreactivity in the human, rat, and dog endocrine pancreas indicates that mammalian IGF-2 and INS genes are regulated simultaneously.
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  • 39
    ISSN: 1619-7089
    Keywords: Positron emission tomography ; Myocardial glucose utilization rates ; Glucose ; Insulin ; Free fatty acids ; Glucagon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The goal of this study was to identify the anatomic and physiologic factors affecting left ventricular myocardial 2-[F-18]fluoro-2-deoxy-d-glucose (FDG) uptake and myocardial glucose utilization rates (MRGlc) in normal humans. Eighteen healthy male volunteers were studied in the fasting state (4–19 h) and 16 after oral glucose loading (100 g dextrose) with positron emission tomography (PET) and FDG. Substrate and hormone concentrations were measured in each study. The kinetics of myocardial FDG uptake were evaluated using both a three-compartment model and Patlak graphical analysis. Systolic blood pressures and rate pressure products were similar in the fasting and postglucose states. MRGlc averaged 0.24±0.17 μmol/min/g in fasting subjects and rose to 0.69±0.11 μmol/min/g after glucose loading. Phosphorylation rate constant, k3, and MRGlc were linearly related (P 〈 0.001). Increases in MRGIc following glucose loading were correlated with plasma glucose, insulin and free fatty acid concentrations, ratios of insulin to glucagon levels, and influx rate constants of FDG. Glucose loading improved the diagnostic image quality due to more rapid clearance of tracer from blood and higher myocardial FDG uptake. When MRGlc, glucose and insulin concentrations, and insulin to glucagon ratios exceeded 0.2 μmol/min/g, 100 mg/dl, 19 μU/ml, and 0.2 μU/pg, respectively, myocardial uptake of FDG was always adequate for diagnostic use. FDG image quality and MRGlc were similar after relatively short (6 ±2 h) and overnight (16 ± 2 h) fasting. Significant (P〈0.05) regional heterogeneity of myocardial FDG uptake and MRGlc was observed in both the fasting and the postglucose studies. MRGlc and FDG uptake values in the posterolateral wall were higher than those in the anterior wall and septum. Thus, both 6-h and overnight fasts resulted in similarly low myocardial glucose utilization rates. While MRGlc and myocardial FDG uptake depended on plasma glucose, free fatty acid, and insulin concentrations, the results also suggest an additional dependency on plasma glucagon levels. Regional heterogeneities in myocardial FDG uptake and MRGlc are evident and independent of the subjects' dietary state. These regional heterogeneities need to be considered in studies of patients with cardiac disease.
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  • 40
    ISSN: 1573-7284
    Keywords: Lipoprotein(a) ; Risk factors ; Blood lipids ; Insulin ; Anthropometry ; Europe
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Serum lipoprotein(a) [Lp(a) ], blood lipids, serum insulin and anthropometric parameters were determined in randomized samples of 38-year-old men living in six European cities: Ede (The Netherlands), Deinze (Belgium), Warsaw (Poland), Lumiar (Portugal), Verona and Naples (respectively in northern and in southern Italy). In total, 406 healthy men were studied. Serum Lp(a), blood lipids and serum insulin were measured in one laboratory. All the anthropometric and metabolic variables considered were statistically different among the participating sites, with the exception of Lp(a) serum levels. In spite of the lack of overall significant inter-center differences (Kruskal-Wallis test), the subjects from the two Italian cities had significantly lower Lp(a) serum levels than the subjects from Belgium and Portugal (Mann-Whitney U test, p 〈 0.01). In all cities the distribution of serum Lp(a) levels were highly skewed; the percentage of subjects with serum Lp(a) levels higher than 30 mg/dl (i.e., the commonly accepted risk level of cardiovascular disease) was 6% in both Verona and Naples (Italy), 12% in The Netherlands, 16% in Poland, 18% in Belgium and 19% in Portugal (for the last two cities, respectively, p 〈 0.02 and p 〈 0.01 vs Italian cities, chi-square test). Neither anthropometric (body mass index, waist/hip circumference ratio) nor metabolic (serum lipids and insulin) parameters showed any significant relationship with serum Lp(a) levels in any of the sites (Spearman's rank correlation). These data support the possibility of a difference in serum Lp(a) levels among different European countries.
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  • 41
    ISSN: 0003-276X
    Keywords: Insulin ; Islet ; Isolation ; Secretion ; Morphology ; Rat ; Immunoassay ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Laboratories engaged in secretory studies of rat pancreatic islets often encounter high baseline insulin secretion with poor secretory response to secretagogues, such as glucose. The specific morphologic abnormalities that accompany this unregulated release have not been described. We isolated islets comparing two approaches. Both used stationary digestion with collagenase. In method I, we distended the biliary duct extracorporeally with collagenase and minced the pancreas after a 28 min digestion (37°C). In method II, we distended the pancreas intracorporeally and digested for 40 min without mincing. Both methods utilized a similar collagenase concentration (2 μg/ml in Hank's balanced salt solution (HBSS)). Both methods yielded over 300 islets/rat. Islets from both methods appeared intact, when viewed under the dissecting microscope. We found that adequate secretion from incubated islets was evoked with method I, i.e., low basal insulin levels at low glucose (3.3 mM), tripling at 11.0 mM glucose, and nearly quadrupling in response to higher glucose (16.7 mM). In contrast, method II was characterized by high basal levels without response to higher glucose. Ultramicroscopic examination of islet B cells in method I revealed normal cytological features, while B cells in method II showed marked degranulation, profiles of swollen endoplasmic reticulum, and swollen mitochondria. Morphometric analysis of B cells confirmed quantitatively a decrease in secretory granule density and mitochondrial enlargement in method II compared to method I. Anatomic changes, largely confined to the B cells of islets may account for functional alterations of responses. Defects cannot be predicted from gross appearance of islets. © 1993 Wiley-Liss, Inc.
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  • 42
    ISSN: 1432-0428
    Keywords: Insulin ; insulin resistance ; testosterone ; androgens ; healthy men ; cardiovascular risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma insulin is a risk factor for diabetes mellitus and cardiovascular disease in men. We investigated the association between plasma testosterone and plasma insulin in an occupational sample of 1292 healthy adult men. Total plasma testosterone decreased with each decade of age and insulin increased with each decade of age. In these cross-sectional data, this significant graded inverse association between testosterone and insulin was independent of age. The association was reduced but not explained by the addition of obesity and subscapular skinfold to the model. Adjustment for alcohol consumption, cigarette smoking and plasma glucose did not materially alter the association. These results are the reverse of the positive association of androgens with insulin in women and suggest alternative possible explanations for the effect of hyperinsulinaemia on cardiovascular disease risk. Prospective studies will be necessary to determine the direction and causal nature of this association.
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  • 43
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    Cellular and molecular life sciences 48 (1992), S. 476-481 
    ISSN: 1420-9071
    Keywords: Insulin ; cyclic GMP ; immunocytology ; Tetrahymena pyriformis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We studied rapid changes in location of cyclic GMP inTetrahymena pyriformis. Insulin caused cGMP localization in cilia and near the plasma membrane (0.5–1 min). Later (1–5 min) cGMP localization was diffuse in cytoplasm with perinuclear accentuation. Inactive insulin analogs did not elicit these changes.
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  • 44
    ISSN: 1432-1254
    Keywords: Heat acclimation ; Insulin ; Brown adipose tissue ; Uncoupling protein ; Cold tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography , Physics
    Notes: Abstract Seventy-one male Wistar strain rats (7 weeks old) were kept at 5, 25, or 34° C, respectively, for 2 weeks with or without insulin administration. Insulin (Novo Lente MC) was given subcutaneously in a dose of 3.62 nmol/125 µl saline per 100 g body weight. An apparent effect of insulin treatment was noted only in heat-exposed rats, resulting in a remarkable gain in inter-scapular brown adipose tissue (BAT) mass of heat-acclimated, insulin-treated rats in terms of weight or weight per unit body weight. The BAT from heat-acclimated, insulin-treated rats had significantly higher levels of protein, DNA, RNA, and triglyceride than BAT from heat-acclimated, saline-treated rats. Therefore, it seems likely that the growth of BAT in heat-acclimated, insulin-treated rats was mostly due to the anabolic effects of insulin. The uncoupling protein mRNA was, however, present in BAT of heat-acclimated, insulin-treated rats at rather a depressed level, explaining a corresponding decrease in cold tolerance. On the other hand, the expression of insulin receptor mRNA was attenuated in BAT of rats from all the insulin-treated groups, possibly due to the down-regulation of insulin. Thus, there appeared to be some linkage among BAT, heat acclimation, and insulin.
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  • 45
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    Pflügers Archiv 422 (1992), S. 267-272 
    ISSN: 1432-2013
    Keywords: Rat ; Myoball ; Potassium channel ; Potassium current ; Sodium current ; Insulin ; Voltage clamp
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A whole-cell early transient outward current occurs in rat myoballs if and only if there is an immediatly preceding current of large amplitude through the voltage-gated, tetrodotoxin-inhibitable Na+ channel. This early outward transient is a K+ current, designated I K(Na+). Under the conditions in which I K(Na+) appears, simultaneous measurement of voltage and current, under voltage clamp, demonstrates that there is transient voltage escape to depolarized levels, peaking at about the time of peak inward Na+ current arid resembling an action potential. I K(Na+) was never seen in the absence of this breach of the voltage clamp, suggesting that I K(Na+) might be an artefact due to transient depolarization from the clamp. However, when the voltage escape was mimicked by voltage commands under conditions in which the Na+ channel was not activated, there was no I K(Na). Insulin increased or produced I K(Na+) even though insulin had no effect on I Na or on the delayed rectifier K+ current or on the escape from voltage clamp. It is concluded that there is a population of rat myoballs in which there is an early outward K+ current that requires an immediately preceding current through the voltagegated tetrodotoxin-inhibitable Na+ channel and is enhanced by insulin.
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  • 46
    ISSN: 1432-1041
    Keywords: Insulin ; Fosinopril ; insulin sensitivity ; glucose tolerance ; lipoproteins ; ACE inhibition ; normal humans ; blood pressure ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of the new ACE-inhibitor, fosinopril, on insulin sensitivity (SI), glucose homoeostasis and lipid profile has been examined in 24 young, healthy, normotensive men. SI, fasting plasma glucose and insulin, serum total triglycerides (Tg) and lipoprotein cholesterol (C) fractions, and ACE activity were assessed after subjects had taken placebo for 1 week and after 3 further weeks either on placebo (12 subjects) or fosinopril 20 mg daily (12 subjects), administered in a doubleblind, randomized order. Measurements were made after 3 days on a standard diet (2500 kcal/d, 45% carbohydrates, 40% fat and 15% proteins) and after an over-night fast. Compared with control values at the end of the runin placebo phase, fosinopril reduced plasma ACE activity (from 106 to 24 nmol·ml−1·min−1), Significantly increased plasma potassium and lowered upright systolic blood pressure. It also improved the k-value of the glucose disappearance rate after glucose load (from −1.70 to −1.88%·min−1) and tended to increase SI slightly although not significantly (from 10.2 to 12.0·10−4·min−1·μU−1·ml−1). Fasting plasma glucose, insulin, serum total, high-, low-, and very-low density lipoprotein cholesterol fractions and total triglycerides were unchanged following fosinopril and placebo. The findings indicate that in healthy lean humans, ACE inhibition with fosinopril is neutral with regard to lipoprotein and carbohydrate metabolism, and that it may slightly enhance cellular glucose disposal. This calls for further evaluation in individuals at high risk of developing insulin resistance and in patients with impaired insulin sensitivity related to hypertension, obesity, decreased glucose tolerance and diabetes mellitus.
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  • 47
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    European journal of clinical pharmacology 42 (1992), S. 453-455 
    ISSN: 1432-1041
    Keywords: Insulin ; Atrial natriuretic factor ; natriuresis ; healthy volunteers ; renal function ; sodium metabolism ; water metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Changes in plasma insulin in response to a physiological or pathophysiological elevation in circulating atrial natriuretic factor (ANF) have been investigated. Plasma insulin, glucose, immunoreactive (ir) ANF, effective renal plasma flow (ERPF), glomerular filtration rate (GFR), absolute and fractional excretion of sodium (FENa), have been measured in 14 volunteers before and during infusion of low doses of ANF or vehicle (V). Each subject received single-blind in a randomized sequence at 2 week-intervals: V alone, or ANF 4, 8 and 16 ng·kg−1·min−1, indused over 90 min. Plasma irANF was increased 2.5- to 11-fold during the ANF infusion as compared to the test with the vehicle. Plasma insulin did not change during V administration (baseline vs V: 22 vs 21 μU·ml−1) and was unchanged during ANF at 4, 8 and 16 ng·kg−1·min−1 (19, 19, 21 μU·ml−1, respectively). Blood pressure, ERPF and GFR were not affected, and diuresis, FENa and urinary Na excretion were increased significantly and dose-dependently during ANF, but not V infusion. Compared to baseline, ANF 4, 8 and 16 ng·kg−1·min−1 increased urinary Na excretion by 147, 241 and 446 μmol·min−1, respectively. The findings indicate that, in normal humans, an acute increase in irANF within or slightly above the physiological range, which modified natriuresis and diuresis, did not alter circulating plasma insulin.
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  • 48
    ISSN: 1432-1041
    Keywords: Insulin ; Non-insulin-dependent diabetes ; Glibenclamide ; combined treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of a subcutaneous injection of an intermediate-acting insulin at bedtime combined with glibenclamide has been evaluated in 16 non-insulin-diabetic patients with secondary failure to respond to oral agents. The patients showed poor metabolic control (HbA1〉11%) after two months on diet and glibenclamide treatment (15 mg.day−1). For 3 months the glibenclamide was continued together with an injection of an intermediate-acting insulin at bedtime in order to maintain fasting blood glucose under 120 mg.dl−1. A significant reduction in fasting blood glucose and HbA1 (15.50 vs 10.35%) and fructosamine (2.03 vs 1.69 mmol.l−1) was observed (230 to 141 mg.dl−1) at a mean insulin dose of 0.28 U.kg−1. The peak blood glucose after a standard test meal was also significantly improved (290 vs 203 mg.dl−1). Two months after the bedtime insulin injection had been withdrawn, only one patient was still being treated with oral agents alone. Except for another patient who dropped out, all the others had to be treated again with insulin because their fasting blood glucose exceeded 180 mg.dl−1. It is concluded that a single subcutaneous injection of an intermediate-acting insulin at bedtime combined with glibenclamide improved fasting and post-meal blood glucose concentrations in non-insulin-dependent patients resistant to diet and oral hypoglycaemic treatment. Almost all of the patients relapsed after insulin was withdrawn.
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  • 49
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    Archives of microbiology 157 (1992), S. 451-456 
    ISSN: 1432-072X
    Keywords: Acinetobacter calcoaceticus ; Periplasm ; Insulin ; cleaving proteinase ; Protease Pi ; Protease III ; Substrate specificity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Cells of Acinetobacter calcoaceticus contain a constitutive periplasmic metalloproteinase showing similar properties as the periplasmic metalloproteinase of Escherichia coli. The periplasmic proteinase of A. calcoaceticus was purified, starting from periplasm, by ammonium sulfate precipitation, hydrophobic interaction chromatography and chromatofocusing up to the homogeneity of the enzyme in SDS-electrophoresis with a yield of 6.7% and a purification factor of 417. The enzyme has a molecular mass of 108000 (gel filtration) or 112000 (native electrophoresis), and consists of four identical subunits with a molecular mass of 27 000 (SDS-electrophoresis). The purified enzyme degrades preferentially polypeptides such as glucagon and insulin. Larger proteins are accepted as substrates to a considerably lower extent. All tested synthetic substrates with trypsin, chymotrypsin, elastase and thermolysin specificity were not cleaved. Therefore, the described enzyme was designated “insulin-cleaving proteinase” (ICP).
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  • 50
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    Acta diabetologica 29 (1992), S. 186-190 
    ISSN: 1432-5233
    Keywords: Diabetes ; Hypertension ; Insulin ; Red blood cell ; Sodium-lithium countertransport ; Sodium-proton exchange
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The presence in human red blood cells (RBC) of insulin receptors led us to examine the role of insulin in the regulation of Na/Li and Na/H exchanges (EXCs) that we previously reported to have high activity in hypertension and diabetic nephropathy. To this end, red cells of fasted normotensive subjects were incubated for 1 h with insulin (0–100 μU/ml) to study the external Na+ activation at ten Na+ concentrations. We found that insulin increased twofold theK m for Na+ to activate Na/H and Na/Li EXC. Insulin also modulated the activity of Na/Li EXC in vivo because theK m for Na was significantly higher in the fed than in the fasted state. In the fed state the highK m for Na+ caused an incomplete saturation of Li+ efflux between 70 and 150 mM Na+ which led to underestimation of theV max andK m. To correctly determine theV max andK m for the extracellular Na+ of Na/Li EXC it is critical to control the feeding status of cases and controls and to ensure complete saturation of the flux. We have studied the Na+-activation kinetics of Na/Li EXC in fed normoalbuminuric and nephropathic patients, raising Na+ concentrations up to 280 mM under isosmotic conditions to avoid cell shrinkage. Under such conditions, Na/Li EXC shows significantly higherK m andV max values in nephropathic than in normoalbuminuric patients; this finding may explain the different results obtained by others in fed diabetic patients. The kinetic alterations of Na/Li EXC are also shared by patients with insulin-resistant hypertension as well as by red blood cells of fasted control subjects exposed in vitro to insulin action. We propose, therefore, that hyperinsulinaemia and/or a hyper-responsiveness of this Na+ antiporter to insulin are linked to the phenotypic alterations of Na/Li EXC in diabetes and hypertension.
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  • 51
    ISSN: 1432-0878
    Keywords: Amylin ; Calcitonin gene-related peptide ; Exocrine and endocrine pancreas ; Insulin ; Islet cells ; Nerve fibers ; Somatostatin ; Mammals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In the pancreas, calcitonin gene-related peptide (CGRP) immunoreactivity has been described in nerve fibers and in distinct types of islet cells. This unique, apparently species-specific cell-type expression prompted the present investigation to clarify further the pattern of CGRP immunoreactivity in different mammalian species (i.e., different strains of rats, mice, guinea pigs, rabbits, cats, dogs, pigs, and humans) commonly used for functional and anatomical studies of the pancreas by means of immunohistochemistry using three different CGRP antibodies. In each species, CGRP-immunoreactive neurites innervate the exocrine and endocrine compartments, the vasculature, and the intrapancreatic ganglia, where they form dense networks encircling unstained cell bodies. The only exception is the pig pancreas, where the islets appear to be devoid of immunoreactive fibers. The overall density of immunoreactive pancreatic axons in different species is as follows: rat, mouse, and rabbit〉guinea pig≥pig and cat〉 〉dog and human. CGRP-immunoreactive endocrine cells appear to be restricted to the rat pancreas, where they form a subpopulation of somatostatin-containing D cells. In contrast, in mouse, guinea pig, cat, dog, and human pancreas, a homogeneous staining of the core of the islets, where insulin-producing B cells are located, was visualized in sections incubated with the rabbit CGRP antiserum at 4°C, but not at 37°C (an incubation temperature that does not affect the islet cell staining in the rat nor the fiber labeling in any species). Furthermore, the staining of islet B cells was not reproductible with all the CGRP antibodies used, all of which comparably stain nerve fibers in each species, and islet D cells in the rat. Immunoreactive islet cells were not visualized in pig and rabbit pancreas. These results are consistent with the hypothesis that the expression of CGRP in nerve fibers is a common feature of mammalian pancreas, whereas its expression in endocrine cells appears to be restricted to the D cells of the rat pancreas.
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  • 52
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    European journal of applied physiology 64 (1992), S. 345-349 
    ISSN: 1439-6327
    Keywords: Adipocyte ; Adrenaline ; Detraining ; Glycerol ; Insulin ; Lipogenesis ; Lipolysis ; Training
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The rates of lipolysis and lipogenesis in adipocytes, isolated from biopsy samples of subcutaneous fat, was assessed by estimation of glycerol release during a 30-min incubation, and of the incorporation of13C-glucose into lipids during a 1-h incubation at 37° C, respectively. The subjects were six highly-qualified, active endurance sportsmen, eight former endurance sportsmen of international class, and six untrained young men. In the active sportsmen the basal rate of lipolysis was about half of that in the previously-active sportsmen and the untrained subjects, but after the addition of adrenaline (10−4 or 5 × 10−4 mol · l−1) the lipolysis rate was the highest. No differences were observed in the lipolytic rates in the former sportsmen compared to the untrained subjects. Gases of a comparatively high level of lipogenesis were found in the trained subjects. The addition of insulin (9 μU · ml−1) to isolated adipocytes caused a significant augmentation of individual rates of lipogenesis in the active sportsmen and the untrained persons but not in the previously-active sportsmen. In comparison with the active sportsmen, the previously active sportsmen revealed an increased basal rate of lipolysis and a reduced sensitivity to the lipogenic action of insulin. These findings suggest that these changes may have had significance in avoiding an increase of adipose tissue after a decrease in energy expenditure due to a change in physical activity.
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  • 53
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    European journal of epidemiology 8 (1992), S. 134-135 
    ISSN: 1573-7284
    Keywords: Insulin ; Atherosclerosis ; Smooth muscle cell ; Endothelial cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A number of processes are involved in the pathogenesis of atherosclerosis. These include an “injury” to the endothelial cell barrier of the inner lining of the artery, infiltration of the artery by lipid filled monocyte-macrophages, proliferation of smooth muscle cells, synthesis of connective tissue and thrombus formation. Insulin may be involved in several of these processes. Over 40 years ago it was shown that insulin is necessary for the production of experimental atherosclerosis in cholesterol fed, alloxan diabetic rabbits. Insulin inhibits regression and stimulates formation of lipid containing lesions in a number of species, and can promote lesions in animals fed normal diets. Insulin is also related to lipid metabolism in the artery wall and interacts with blood pressure to stimulate lipid synthesis in arteries. Arterial smooth muscle cells cultured from a number of species including humans proliferate in response to levels of insulin similar to those found in normal human physiology. The proliferative effects of insulin are mediated by the insulin-like growth factor receptor and hence may not be impaired in states of insulin resistance. Insulin also stimulates arterial smooth muscle cell migration. Insulin stimulates cholesterol synthesis in cultured smooth muscle cells and enhances LDL receptor activity in a number of cell types. Insulin stimulates connective tissue synthesis, and promotes clotting.
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  • 54
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    Pharmacy world & science 14 (1992), S. 253-257 
    ISSN: 1573-739X
    Keywords: Contraceptive steroids ; Hormone delivery systems ; Insulin ; Oestrogen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Some new concepts in the delivery of hormones are described. Transmucosal or transdermal penetration of hormones can be facilitated, often by the use of absorption enhancers. Studies of nasal insulin delivery are described. Recently developed iontophoretic delivery devices can be useful for pulsatile transdermal administration of peptide hormones. A self-regulating delivery system releasing insulin in response to glucose levels is described. A vaginal ring relasing ethinylestradiol and 3-ketodesogestrel is a new concept in long-acting contraception. A nasal estradiol formulation, containing the absorption enhancer dimethyl-β-cyclodextrin, is an interesting alternative to oral and transdermal delivery of female sex hormones.
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  • 55
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    Cellular and molecular life sciences 47 (1991), S. 270-272 
    ISSN: 1420-9071
    Keywords: Insulin ; potassium ; hyperkalemia ; portal vein ; glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The effect of hyperkalemia on insulin secretion remains undefined. We evaluated portal and peripheral insulin levels in anesthetized dogs after infusions of KCl. The mean maximal increase in peripheral plasma potassium at infusion rates of 0.2 mEq/kg/h was 0.68±0.20 mEq/l. There were no significant increases in either portal or peripheral insulin levels. In contrast, in six dogs whose plasma potassium concentration increased in each case by more than 2.0 mEq/l (infusion rate of 0.5 mEq/kg/h), portal insulin levels increased fivefold (p〈0.05). We conclude that only marked increases in plasma potassium concentration stimulate pancreatic insulin secretion.
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  • 56
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    Journal of molecular medicine 69 (1991), S. 31-36 
    ISSN: 1432-1440
    Keywords: (D-)ribose ; Glucose ; Insulin ; C-peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary D-ribose was given orally and/or intravenously to nine healthy subjects at doses ranging from 83.3 to 222.2 mg/kg per hour for at least four hours. The serum ribose level increased in a dose-dependent manner to maximum concentrations of 75 to 85 mg/dl. The serum glucose level decreased after the beginning of continuous ribose administration and was reduced as long as ribose was being administered. The oral or intravenous administration of 166.7 mg/kg per hour of ribose resulted in a 25% decrease in serum glucose. Higher intravenous doses of ribose did not provoke a further decrease in serum glucose concentration. Oral administration of 166.7 mg/kg per hour led to an increase in serum insulin concentrations from a mean of 8.4 (range 6.4–11.5) to 10.4 (range 6.3–15.4) μU/ml (p〈0.05). In contrast, intravenous administration did not change serum insulin concentrations significantly. The serum c-peptide concentration remained unchanged regardless of treatment. We conclude that the variations in plasma insulin concentrations do not account for the observed decrease in mean serum glucose concentrations accompanying D-ribose administration.
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  • 57
    ISSN: 1432-0428
    Keywords: Insulin ; glucose ; obesity ; glucose disposal ; insulin secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin responses to intravenous glucose infusion and glucose utilization during hyperinsulinaemic euglycaemic clamp were determined in a large homogeneous group of 65-year-old male subjects. Twenty-eight had untreated Type 2 (non-insulin-dependent) diabetes mellitus and the remaining 44 control subjects had a normal glucose tolerance. Diabetic patients with abdominal obesity displayed peripheral insulin resistance in combination with defective insulin secretion, whereas non-obese diabetic patients showed only a secretory defect. Thus, Type 2 diabetes in obese and non-obese elderly male subjects may take two forms where the cause of hyperglycaemia differs.
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  • 58
    ISSN: 1432-0428
    Keywords: Insulin ; glucose ; insulin resistance ; man ; glucotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In vitro and in vivo studies have suggested that metabolic deterioration can be induced by hyperglycaemia per se. The effect of 53 h of 2.2 mg glucose · kg ideal body weight−1· min−1 was examined in four normal male subjects. This produced overnight hyperglycaemia of 6.0 mmol/l on the two nights of the study compared with 4.7 mmol/l on the control night (p〈0.05). In response there was a sustained, two-fold increase in basal plasma insulin (p〈0.005) and C-peptide (p〈0.05) levels. After two days of hyperglycaemia an increased Beta-cell response was demonstrated in response to an additional glucose infusion stimulus (estimated Beta-cell function median of 84% on the control day to 100% after two days glucose infusion). Plasma insulin and C-peptide responses to a 10.0 mmol/l hyperglycaemic clamp increased over the two days of the study (insulin from median 48 mU/l to 73 mU/l and C-peptide from median 2.0 pmol/ml to 2.6 pmol/ml). Glucose tolerance to the additional glucose infusion stimulus improved, suggesting that the increased insulin response during hyperglycaemia was enhancing peripheral glucose uptake. The calculated peripheral insulin sensitivity was unchanged during the hyperglycaemic clamp. Thus, in response to the two days of basal hyperglycaemia, both the basal and stimulated Beta-cell responses were enhanced and there was no evidence for ‘glucose toxicity’ to the Beta-cells.
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  • 59
    ISSN: 1432-0428
    Keywords: Insulin ; hepatic clearance ; receptor recycling ; receptor-mediated endocytosis ; physiological model ; mouse liver perfusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary After perfusion of mouse livers with A14-125I-insulin for designated intervals, an acid-wash technique was employed to separately measure the surface-bound (Xs) and intracellular (Xi) A14-125I-insulin, as well as intracellular degradation products (Xdeg) of labelled insulin. From the perfusate concentrations (Cp) of A14-125I-insulin, the apparent intrinsic hepatic clearance of labelled insulin at a high dose (0.2 nmol/l) was shown to be 60% smaller than that at a low dose (0.018 nmol/l), indicating that the cellular uptake of insulin is remarkably nonlinear at the concentration range examined. From the time courses of Cp, Xs, Xi and Xdeg, the hepatic insulin disposition was shown to be largely accounted for by the receptor-mediated endocytosis. The observed data at the low dose were analysed to estimate biochemical parameters, (i.e., total receptor number, endocytotic rate constant and intracellular degradation rate constant) according to “receptor-recycling” and “non-receptor-recycling” models, using a computer-aided optimization procedure. The “receptor-recycling” model could not only adequately explain the Cp, Xs, Xi and Xdeg at the low dose, but also predict the Cp at the high dose. On the other hand, a “non-receptor-recycling” model, in which recycling of receptors was not assumed, could also explain the observed data at the low dose, but failed to predict the Cp at the high dose, indicating that the receptor recycling process is necessary to explain the hepatic insulin clearance at high insulin concentrations, at which hepatic insulin clearance should be limited by the rate of receptor recycling. However, the applicability of our model might be limited within the physiologic insulin concentrations, because of the negative co-operativity of insulin-receptor interaction and a high-capacity, non-degradative and more rapidly recycling pathway for receptors that may occur at high concentrations of insulin. In conclusion, we have developed a mathematical model of hepatic insulin clearance and distribution under physiological conditions, including receptor binding, receptor-mediated endocytosis and receptor recycling, which has been so far demonstrated using isolated hepatocytes.
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  • 60
    ISSN: 1432-0428
    Keywords: Insulin ; C-peptide ; Glucagon ; Pancreas ; Transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It has been established that successful pancreas transplantation in Type 1 (insulin-dependent) diabetic patients results in normal but exaggerated phasic glucose-induced insulin secretion, normal intravenous glucose disappearance rates, improved glucose recovery from insulin-induced hypoglycaemia, improved glucagon secretion during insulin-induced hypoglycaemia, but no alterations in pancreatic polypeptide responses to hypoglycaemia. However, previous reports have not segregated the data in terms of the length of time following successful transplantation and very little prospective data collected over time in individual patients has been published. This article reports that in general there are no significant differences in the level of improvement when comparing responses as early as three months post-operatively up to as long as two years post-operatively when examining the data cross-sectionally in patients who have successfully maintained their allografts. Moreover, this remarkable constancy in pancreatic islet function is also seen in a smaller group of patients who have been examined prospectively at various intervals post-operatively. It is concluded that successful pancreas transplantation results in remarkable improvements in Alpha and Beta cell but not PP cell function that are maintained for at least one to two years.
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  • 61
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    Diabetologia 34 (1991), S. 144-149 
    ISSN: 1432-0428
    Keywords: Insulin ; insulin-like growth factor I ; euglycaemic clamping ; glucose metabolism ; lipogenesis ; glycogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The acute metabolic actions of insulin-like growth factor I were studied in anaesthetized adult rats and its potency was compared to that of insulin. Following an i. v. bolus injection of insulin-like growth factor I a dose-dependent decrease of blood glucose and serum non-esterified fatty acid concentrations was noted with a potency of about 2% that of insulin. Stimulation of total body glucose disposal during euglycaemic clamping required ∼ 50times higher insulin-like growth factor I serum concentrations to achieve an identical half-maximal response. A similar difference in potency was observed for the stimulatory action on 2-de-oxyglucose uptake and on glycogen formation in skeletal muscle. Lipogenesis in epididymal fat pads was increased dose-dependently by both hormones requiring approximately 30 times higher half-maximally effective serum concentrations of insulin-like growth factor I. These data demonstrate that insulin-like growth factor I exerted acute insulin-like metabolic actions in vivo with low potency. These effects were probably mediated via insulin receptors. A preferential stimulation of glucose metabolism in skeletal muscle was not observed.
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  • 62
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    Diabetologia 34 (1991), S. 868-876 
    ISSN: 1432-0428
    Keywords: Insulin ; fetal rat hepatocytes ; glycogen ; endocytosis ; degradation ; retroendocytosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studied insulin processing and hepatic glycogenesis in cultured hepatocytes isolated from rat fetuses of 17, 19, and 21 days of gestation. Steady-state insulin binding increased by 250% between days 17 and 19, from 145±8 to 361±52 fmol/mg protein, and by an additional 40% (405±69 fmol/mg protein) by 21 days of gestation. At 37°C, 125I-insulin was rapidly (t1/2〈5 min) internalized by hepatocytes at all three ages, reaching maximal levels (63–76% of the total cell-associated radioactivity) by 15 min. 125I-labelled degradation products appeared rapidly (t1/2〈15 min) within the cells. Yet, the majority (68–77%) of the intracellular radioactivity consisted of intact 125I-insulin, even after 4 h at 37°C. Hepatocytes pre-loaded with 125I-insulin and then acid-stripped of surface-bound radioactivity, rapidly released both intact 125I-insulin (retroendocytosis) and its radiolabelled degradation products. While intact insulin was initially released more rapidly (t1/2〈6 min), and reached a plateau after 15–30 min, the degradation products continued to accumulate in the medium for at least 4 h. Methylamine inhibited intracellular 125I-insulin degradation at all three gestational ages and also blocked insulin-stimulated glycogenesis in 19- and 21-day hepatocytes, without altering basal glycogen synthesis. Insulin-stimulated glycogenesis was not induced in 17-day fetal rat hepatocytes in control or methylamine-treated cultures. We conclude that both degradative and retroendocytotic pathways for processing insulin are present in fetal rat hepatocytes by 17 days of gestation. Further, insulin-receptor processing was functionally related to the glycogenic action of insulin in responsive 19- and 21-day fetal rat hepatocytes
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  • 63
    ISSN: 1432-0428
    Keywords: Insulin ; insulin analogues ; insulin-like growth factors ; proliferation ; vascular smooth muscle cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Binding and growth promoting effects of insulin, insulin analogues modified in the B chain, proinsulin, insulin-like growth factor-I and -II were studied in cultured rat aortic smooth muscle cells. Specific binding of125I-insulin was 0.9±0.2% of total 125I-insulin added, and the IC50-value was estimated to 8.9 pmol/1. The insulin analogue B10 Asp tended to be more potent than insulin in displacing 125I-insulin, B28 Asp was equipotent, B9 Asp/B27 Glu was approximately 100 times less potent and insulin-like growth factor-I more than 1000 times less potent than insulin. Specific binding of 125I-insulin-like growth factor-I after 4 h incubation at 10 °C was five times higher than the specific binding of insulin (4.4±0.4% of total 125I-insulin-like growth factor-I added), and the IC50-value was 0.3 nmol/l. Insulin was approximately 500 times less potent than insulin-like growth factor-I in displacing 125I-insulin-like growth factor-I. The insulin analogue B10 Asp was slightly more potent and analogue B28 Asp was equipotent with insulin. Analogue B9 Asp/B27 Glu was ten times less potent and proinsulin was more than ten times less potent than insulin. The order of potency was similar for 3H-thymidine incorporation into DNA: insulin-like growth factor-I 〉 B10 Asp 〉 insulin-like growth factor-II 〉 insulin 〉 B28 Asp 〉 B9 Asp/B27 Glu 〉 proinsulin. The maximal effect of insulin-like growth factor-I on 3H-thymidine incorporation was 71±16% higher than the maximal effect of insulin. The maximal effect of insulin-like growth factor-II was at least as high as the effect of insulin-like growth factor-I. Furthermore, the maximal effect of B10 Asp was 62±10% higher than the maximal effect of insulin. Insulin-like growth factor-I and B10 Asp tended to increase cell number more than insulin. In conclusion, this study shows that insulin analogues interact with different potencies with receptors for insulin and insulin-like growth factor-I in vascular smooth muscle cells and that insulin-like growth factors and the insulin analogue B10 Asp have more pronounced growth effects than insulin. Substitution of the amino acid Asp for His at position B10 in insulin makes the molecule more similar to insulin-like growth factor-I, chemically and probably also biologically.
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  • 64
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    European journal of pediatrics 150 (1991), S. 339-342 
    ISSN: 1432-1076
    Keywords: Glucose tolerance ; Turner syndrome ; Insulin ; GIP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is a well documented increase in the incidence of abnormal glucose tolerance in patients with Turner syndrome. To elucidate the pathophysiology of this phenomenon, we studied the serum concentrations of gastric inhibitory polypeptide (GIP) — as probably the most important hormonal factor of the entero-insular axis — in relation to impaired glucose tolerance in this syndrome. Oral glucose tolerance tests were performed in 12 Turner patients with simultaneous determination of plasma glucose, insulin and GIP. An impaired glucose tolerance (iGT) was found in four patients with a chronological age between 12.3 and 14.9 years. These patients were compared with found Turner patients of similar age and weight and a normal glucose tolerance (nGT). The highest insulin level occurred 90 min after stimulation in the patients with iGT compared to 30 min in the nGT group. Interestingly, the total areas under the insulin curves were not different. Stimulated plasma GIP concentrations and the areas under the GIP curves wer significantly lower in iGT compared to nGT patients. A disturbed entero-insular axis might contribute to the delayed — rather than diminished — release of insulin in patients with Turner syndrome and impaired glucose tolerance.
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  • 65
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    European journal of clinical pharmacology 40 (1991), S. 379-381 
    ISSN: 1432-1041
    Keywords: Insulin ; glibenclamide ; C-peptide ; insulin catabolism ; diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In eight patients with uncomplicated non insulin dependent diabetes mellitus, serum insulin levels, serum C-peptide levels and blood glucose levels were measured before and after oral administration of glibenclamide 0.1 mg/kg body weight and a test meal, or after a test meal alone. The rise in serum insulin levels persisted longer after glibenclamide. The initial rise in serum insulin was of the same magnitude in both situations, as was the rise in serum C-peptide levels during the entire 5 h study. It is concluded that glibenclamide is able to maintain a more protonged increase in serum insulin levels by inhibiting the degradation of insulin in the vascular endothelial cells of the liver. The inhibition contributes to the blood glucose lowering effect of glibenclamide.
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  • 66
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    European journal of pediatrics 150 (1991), S. 554-556 
    ISSN: 1432-1076
    Keywords: Diabetes ; Insulin ; Therapy ; Child
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of our study was to assess whether a non-invasive insulin injector could improve the metabolic control of ten diabetic children complaining of painful injections with syringe and needle. The cumulative study period amounted to 1347 days. Whereas a non-significant rise in insulin needs was observed (from 0.98±0.03 to 1.03±0.06 units/kg per day, mean ± sem), mean HbA1c value remained unchanged (8.9%±0.4% vs 9.0%±0.5%). Jet injections were felt as less painful than those using syringe and needle (nine out of ten cases). This advantage was hampered by side-effects in eight out of ten cases such as episodes of glycoketonuria (six out of ten cases) leading to hospitalization in three patients. Other side-effects included inability to adjust injection pressure (four out of ten cases) and technical failure requiring an exchange of injector in five cases. The four children with most serious problems were significantly younger (P=0.009) than other subjects. In conclusion, this type of injector should be discouraged in young diabetic children. For older children and adolescents, it may be an alternative to syringe and needle provided repeated detailed information and tight medical supervision is available.
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  • 67
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    Journal of cancer research and clinical oncology 117 (1991), S. 416-420 
    ISSN: 1432-1335
    Keywords: Pancreas cancer ; Insulin ; Somatostatin ; Growth ; Colony formation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of insulin and somatostatin on the growth and the colony formation of two human pancreatic cancer cell lines, BxPC-3 and SOJ-6, were studied. The BxPC-3 cell line (American Type Culture Collection no. CRL 1687) was derived from a moderately differentiated pancreatic adenocarcinoma. The SOJ-6 cell line is a subclone of SOJ that was initiated from ascites of a well-differentiated pancreatic adenocarcinoma. Both cell lines express fetoacinar pancreatic antigen, an antigen that might be associated with early transformation stages. However, these lines have different proliferation and tumoral powers. SOJ-6 cells showed an almost twofold higher division rate over BxPC-3 cells when cultured in RPMI-1640 medium containing 10% fetal bovine serum. The tumorigenic degree of SOJ-6 cells, as assessed by tumor growth in nude mice, was about three times greater than that of BxPC-3. The in vitro growth of BxPC-3 cells was significantly promoted by insulin, and was slightly inhibited by somatostatin, whereas the growth of SOJ-6 cells was not influenced by these hormones. Using a clonogenic assay in soft agar, the average ratio of colony numbers formed by SOJ-6 and BxPC-3 was about 10/1, indicating a good correlation between the colony formation and tumorigenic degree in vivo. In this test, the number of colonies formed by BxPC-3 cells was increased about twofold in insulin-supplemented medium. On the other hand, somatostatin inhibited the colony formation by a factor of four to six. However, no hormonal modulation of the colony formation of SOJ-6 cells was observed. Our data show that pancreatic cancer cell lines respond differently to pancreatic hormones, and suggest that this may be correlated to a tumour stage or a tumour type.
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  • 68
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    Journal of biomolecular NMR 1 (1991), S. 237-246 
    ISSN: 1573-5001
    Keywords: Linear prediction ; Heteronuclear correlation ; 2D NMR spectra ; Protein ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Linear prediction has been used to extrapolate the t1 domain of natural abundance1H−13C correlated two-dimensional (2D) FIDs of insulin. The FIDs were obtained by two different heteronuclear correlation experiments, one that utilizes heteronuclear multiple-quantum coherence during t1, and one that utilizes13C single-quantum coherence. It is shown that the enhancement of the resolution and sensitivity in the F1 dimension of the Fourier transform spectrum that results from the linear prediction extrapolation allows the t1 domain to be confined to a relatively short time period where the signal intensity is at maximum. In particular, it is found that the enhancement thus obtained is sufficiently good to allow an observation of the difference between the F1 line widths in the single-quantum and double-quantum coherence spectra.
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  • 69
    ISSN: 1432-5233
    Keywords: Insulin ; C-peptide ; Glucose ; Glipizide ; Non-insulin-dependent diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of a rapid-acting sulphonylurea, glipizide, on the dose-response relationship between the β-cell response (insulin and C-peptide secretion) and the ambient plasma glucose concentration was examined in 12 healthy and 6 non-insulin-dependent diabetic subjects. The subjects participated in two sets of experiments which were performed in random order: (A) four hyperglycaemic clamp studies, during which the plasma glucose concentration was raised for 120 min by 1 (only in healthy subjects), 3, 7, and 17 mmol/l; and (B) the same four hyperglycaemic clamp studies preceded by ingestion of 5 mg glipizide. All subjects participated in a further study, in which glipizide was ingested and the plasma glucose concentration was maintained at the basal level. In control subjects in the absence of glipizide, the firstphase plasma insulin response (0–10 min) increased progressively with increasing plasma glucose concentration up to 10 mmol/l, above which it tended to plateau. Glipizide augmented the first-phase insulin response without changing the slope of the regression line relating plasma insulin to glucose concentrations. The second-phase plasma insulin response (20–120 min) increased linearly with increasing hyperglycaemia (r=0.997). Glipizide alone increased the plasma insulin response by 180 pmol/l. A similar increase in plasma insulin response following glipizide was observed at each hyperglycaemic step, indicating that glipizide did not affect the sensitivity of the β-cell to glucose. First-phase insulin secretion was reduced in the type 2 (non-insulin-dependent) diabetic patients, and was not influenced by glipizide. The dose-response curve relating second-phase insulin secretion to the ambient plasma glucose concentration was significantly (P〈0.001) flatter in the diabetic patients than in the control subjects. Glipizide alone increased the plasma insulin response by 60 pmol/l without changing the slope of the dose-response curve. It is concluded that, in both type 2 diabetic patients and healthy subjects: (A) sulphonylurea augments glucose-stimulated second-phase insulin secretion without changing the sensitivity of the β-cell to glucose; (B) first-phase insulin secretion is reduced in non-insulin-dependent diabetic patients with fasting hyperglycaemia and is not influenced by sulphonylurea.
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  • 70
    ISSN: 1432-0878
    Keywords: B cells ; Insulin ; Catecholamine ; synthesizing enzymes ; Immunohistochemistry ; Chicken
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The identity of the monoamine which produces a very weak formaldehyde-induced fluorescence in some pancreatic islet cells was studied by fluorescence microscopy and immunohistochemistry either on the same tissue section or on serial tissue sections of tissue from male chickens. Pancreatic islet cells showing this very weak formaldehyde-induced fluorescence react immunohistochemically with antisera directed against insulin, aromatic L-amino acid decarboxylase and dopamine beta-hydroxylase and therefore appear to be islet B cells producing insulin and noradrenaline.
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  • 71
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    Cell & tissue research 265 (1991), S. 261-273 
    ISSN: 1432-0878
    Keywords: Endocrine pancreas ; Immunization ; Insulin ; Glucagon ; Somatostatin ; Electron microscopy ; Rabbit (Chinchilla, Ch: b Ch)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary An active or passive immunization against hormones and the subsequent neutralization of hormones by circulating antibodies is a valuable tool for the identification of hormonal action. To recognize presumed local (autocrine, paracrine) effects exerted by pancreatic hormones, the endocrine pancreas of rabbits was investigated electron-microscopically after long-term immunization against glucagon or somatostatin. Glucagon immunization resulted in hyperplasia and hypertrophy of glucagon- (A-) cells and in their increased metabolic activities: They showed prominent nucleoli, increased amounts of endoplasmic reticulum, Golgi areas, and mitochondria. These changes were paralleled by alterations in secretion granules (increased size, decreased hormonal content), increased numbers of lysosomes (crinophagic bodies), and an increment of the filamentous system. Basically, these findings point to an autocrine regulation of A-cells. Following somatostatin immunization, somatostatin- (D-) cells were hyperplastic but unchanged in their metabolic state. Instead, insulin-(B-) cells and A-cells exhibited equivalents of increased cellular activities (parameters, see above). This stimulation most probably is caused by cancelled paracrine (inhibitory) effects of somatostatin. The changes observed after both immunizations were differently expressed in morphologically heterogeneous islet types (size, angioarchitecture, cellular composition, microtopology of the various cell types). It is concluded, therefore, that the regulation of islets is not uniform. Autocrine and paracrine effects exerted by islet hormones are of different significance in individual islets, or they interfere differently with other regulatory signals.
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  • 72
    ISSN: 1619-1560
    Keywords: Postprandial hypotension ; Elderly ; Carbohydrate ; Neurotensin ; Catecholamines ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies have demonstrated that blood pressure falls postprandially in fit elderly subjects, the greatest changes occurring after meals with a high carbohydrate content. To evaluate the influence of the type of carbohydrate on postprandial blood pressure, the effects of equivalent energy content (2.4 MJ) high complex (starch) and high simple (monosaccharide) carbohydrate meals were studied in seven healthy elderly subjects. Blood pressure, heart rate, autonomic function, plasma catecholamines, insulin and neurotensin levels were measured pre- and postprandially. Greater falls in supine and erect systolic blood pressure occurred after the high simple than the high complex carbohydrate meal (p 〈 0.05). No differences were found in supine or erect diastolic blood pressure, heart rate or in any of the biochemical parameters measured between the meal types. It is concluded that a simple carbohydrate meal results in a greater postprandial fall in blood pressure than an equivalent energy complex carbohydrate meal in the elderly, although the mechanisms for these changes are unknown.
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  • 73
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    European journal of applied physiology 62 (1991), S. 286-291 
    ISSN: 1439-6327
    Keywords: High altitude ; Cortisol ; Insulin ; Growth hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Concentrations of glucose, lactic acid, free fatty acid (FFA), insulin, cortisol and growth hormone (GH) in the blood were monitored in 15 euglycaemic men (sojourners, SJ) at sea level (SL) and while at altitudes of 3500 m and 5080 m, in acclimatised low landers (ALL) and in high altitude natives (HAN). In SJ, blood glucose and insulin concentrations showed a significant increase on the 3rd and 7th day after arrival at high altitude (HA), thereafter returning to sea level values and remaining the same during the entire period of their stay at 3500 m. Subsequently, on arrival at higher altitude (5080 m) the glucose concentrations again showed an increase over the preceding values and returned to SL values on day 41 while at 5080 m. A significant increase in cortisol concentrations was seen on day 3 after arrival at HA and the increased levels were maintained until day 21 at 3500 m. The cortisol concentrations on day 30 after arrival at 5080 m came down to SL values and remained unchanged thereafter. No appreciable change in GH and FFA was seen during the sojourn at HA. On the other hand, blood lactic acid concentration decreased significantly. There was no difference between the fasting glucose concentrations in ALL at 3500 m and in HAN at 3500 m and 4200 m compared to values of SJ at SL, whereas ALL at 4200 m had higher glucose values. Concentrations of plasma insulin and GH in ALL and HAN were higher than the values of SJ at SL, whereas cortisol values did not show any difference. These observations indicated that at HA the glucose values were high for the insulin concentration observed and might have been due to increased secretion of GH by the pituitary gland.
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  • 74
    ISSN: 1439-6327
    Keywords: Endurance conditioning ; Aerobic fitness ; Lipoproteins ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two experiments were carried out to compare the cardiorespiratory and metabolic effects of cross-country skiing and running training during two successive winters. Forty-year-old men were randomly assigned into skiing (n = 15 in study 1,n = 16 in study 2), running (n = 16 in study 1 andn = 16 in study 2) and control (n = 17 in study 1 andn = 16 in study 2) groups. Three subjects dropped out of the programme. The training lasted 9–10 weeks with 40-min exercise sessions three times each week. The training intensity was controlled at 75%–85% of the maximal oxygen consumption (VO2max) using portable heart rate metres and the mean heart rate was 156–157 beats·min−1 in the training groups. In the pooled data of the two studies the mean increase in theVO2max (in ml·min−1·kg−1) on a cycle ergometer was 17% for the skiing group, 13% for the running group and 2% for the control group. The increase inVO2max was highly significant in the combined exercise group compared to the control group but did not differ significantly between the skiing and running groups. The fasting serum concentrations of lipoproteins and insulin did not change significantly in any of the groups. These results suggested that training by cross-country skiing and running of the same duration and intensity at each session for 9–10 weeks improved equally the cardiorespiratory fitness of untrained middle-aged men.
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  • 75
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    European journal of applied physiology 63 (1991), S. 48-51 
    ISSN: 1439-6327
    Keywords: Insulin ; Hyperglycemia ; Hyperinsulinemia ; Human subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The purpose of the present investigation was to examine the effects of hyperglycoemia induced by supramaximal exercise on blood glucose homeostasis during submaximal exercise following immediately after. Six men were subjected to three experimental situations; in two of these situations, 3 min of high-intensity exercise (corresponding to 112, SD 1%VO2 max) was immediately followed by either a 60-min period of submaximal exercise (68, SD 2%VO2 max) or a 60-min resting period. In the third situation, subjects performed a 63-min period of submaximal exercise only. There were no significant differences between the heurt rates, oxygen uptakes, and respiratory exchange ratios during the two submaximal exercise bouts (〉 15 min) whether or not preceded by supramaximal exercise. The supramaximal exercise was associated within 10 min of the start increases (P〈0.05) in blood glucose, insulin, and lactate concentrations. This hyperglycemia was more pronounced when subjects continued to exercise submaximally than when they rested (at 7.5 min;P〈0.05). There was a more rapid return to normal exercise blood glucose and insulin values during submaximal exercise compared with rest. The data show that the hyperinsulinemia following supramaximal exercise is corrected in between 10–30 min during submaximal exercise following immediately, suggesting that this exercise combination does not lead to premature hypoglycemia.
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  • 76
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    European journal of applied physiology 63 (1991), S. 417-423 
    ISSN: 1439-6327
    Keywords: Energy expenditure ; Thermogenesis ; Epinephrine ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The contribution of insulin (3.6 pmol sd kg body mass−1·min−1 to adrenaline-induced (0.164 nmol · kg fat free mass−1·min−1) thermogenesis was studied in ten postabsorptive healthy volunteers using two sequential protocols. Variables considered were oxygen consumption as well as carbon dioxide production, heart rate, blood pressure, plasma concentrations of glucose, insulin, glycerol, free fatty acids,β-HO-butyrate and lactate. Adrenaline increased plasma concentrations of glucose, glycerol, free fatty acids, andβ-HO-butyrate, and heart rate and metabolic rate during normo-insulinaemia [61.3 (SEM 6.6) pmol·−1]. Similar effects were observed during hyperinsulinaemia [167.9 (SEM 18.7) pmol·−1], but the effect of adrenaline on oxygen consumption was reduced. On average, metabolic rate increased by 12.9% during normo-insulinaemia and by 8.9% during hyperinsulinaemia. We concluded that relative hyperinsulinaemia resulted in decreased adrenaline-induced thermogenesis and therefore increased whole body anabolism.
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  • 77
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    European journal of applied physiology 63 (1991), S. 242-249 
    ISSN: 1439-6327
    Keywords: Atropine ; Glucose ; Fructose ; Dietary thermogenesis ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Muscarinic blockade by atropine has been shown to decrease the thermic effect of a mixed meal, but not of intravenous glucose. To further delineate the mechanisms involved in the atropine-induced inhibition of thermogenesis after a meal, plasma substrate and hormone concentrations, energy expenditure (EE) and substrate oxidation rates were measured before and during a continuous glucose infusion (44.4 μmol·kg−1·min−1) with or without atropine. After 2 h of glucose infusion, a 20-g oral fructose load was administered while the glucose infusion was continued. Plasma insulin concentrations attained a plateau at 596 (SEM 100) pmol·l−1 after 120 min of glucose infusion and were not affected by muscarinic blockade; plasma glucose concentrations peaked at 13.3 (SEM 0.5) mmol·l−1 at 90 min and decreased progressively thereafter; no difference was observed with or without atropine. Plasma free fatty acid and glucagon concentrations, with or without atropine, were both decreased to 201 (SEM 18) μmol·l−1 and 74 (SEM 4) ng·l−1, respectively, after 2 h of glucose infusion, and were not further suppressed after oral fructose. Carbohydrate oxidation rates (CHOox) increased to 20.8 (SEM 1.4) μmol·kg−1·min−1 and lipid oxidation rates (Lox) decreased to 1.5 (SEM 0.3) μmol·kg−1·min−1 between 90 and 120 min after the beginning of glucose infusion and were not affected by atropine. Glucose-induced thermogenesis was similar with [6.5% (SEM 1.4%) of basal EE] or without [6.0% (SEM 1.0%), NS) muscarinic blockade during the 30 min preceding fructose ingestion. During the second half-hour after fructose ingestion, atropine infusion inhibited markedly the stimulation of CHOox [+2.8 (SEM 1.0) μmol·kg−1·min−1 vs +6.9 (SEM 1.0) μmol·kg−1·min−1, saline, P〈0.02] and the suppression of Lox [−0.8 (SEM 0.2) μmol·kg−1·min−1 vs −1.4 (SEM 0.2) μmol·kg−1·min−1, saline, P〈0.05]. Carbohydrate-induced thermogenesis during the second half-hour after fructose ingestion, increased to 13.0% (SEM 2.0%) without atropine and was suppressed to 7.7% (SEM 1.9%) (P〈 0.05, vs saline) with atropine. It was concluded that muscarinic blockade suppressed the increase of thermogenesis observed after oral fructose, but not during intravenous glucose infusion and that this suppression occurred independently of alterations of plasma insulin concentrations.
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  • 78
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    Molecular Reproduction and Development 29 (1991), S. 253-258 
    ISSN: 1040-452X
    Keywords: Embryos ; Insulin ; ICM ; Trophectoderm ; Receptor ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: Insulin specifically stimulates protein synthesis in compacted mouse embryos on days 3 and 4 after fertilization, with an EC50 of 0.5 pM (Harvey and Kaye, 1988). The identity of the receptor mediating this short-term effect of insulin was further examined by dose-response studies with IFG-1 and by using a specific anti-insulin receptor antiserum that has no appreciable cross-reaction with IGF-1 receptors. IGF-1 caused a maximum 40% stimulation of protein synthesis after 4 h exposure (similar to the response to insulin) with an EC50 of 150 pM IGF-1. The insulin receptor-specific antiserum, or IgGs isolated from it, also stimulated protein synthesis at dilutions as high as 1:1,000 to the same degree as insulin (∼40%). This agonistic action of the insulin receptor antiserum, the EC50 of 150 pM for IGF-1, and the previously established EC50 of 0.5 pM for insulin, all with similar maximal stimulation, strongly support the conclusion that the short-term metabolic stimulation of mouse blastocysts by insulin is mediated by insulin receptors. Immunosurgical isolation of inner cell masses before and after exposure to 1.7 pM insulin (sufficient to stimulate only the insulin receptor) showed that insulin stimulates protein synthesis in these cells as well as in the trophectoderm cells of the blastocyst. This finding suggests that in intact blastocysts, insulin may travel across the trophectoderm to the inner cell mass, acting anabolically on both tissues. Analysis of the agonistic effect of the B-10 antiserum showed there was no evidence of an unresponsive subpopulation of embryos.
    Additional Material: 6 Ill.
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  • 79
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    Journal of anesthesia 4 (1990), S. 131-137 
    ISSN: 1438-8359
    Keywords: Arterial keton body ratio ; Insulin ; Β-Hydroxybutyrate ; Upper abdominal surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The relationship between the arterial keton body ratio (AKBR: acetoacetate/Β-hydroxybutyrate) and the plasma hormone activities were studied under a general anesthesia using enflurane group (group G) and a GO + Epidural group (group E) with continuous glucose loading (10 g·hr−1) during partial gastrectomy. In both groups, the AKBR increased significantly during the operation. The plasma insulin activity was significantly positively correlated with the AKBR and it was negatively correlated with log (Β-hydroxybutyrate) in both groups. We could not find any significant difference of the AKBR between group G and group E. Our results indicate that the plasma insulin activity affects the arterial keton body ratio and that the AKBR must be evaluated considering the plasma hormone activity, especially insulin activity during the operation. (Ogata M, Obata K, Matsumoto et al.: The changes in arterial keton bodies during upper abdominal surgery. J Anesth 4: 131–137, 1990)
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  • 80
    ISSN: 1432-0428
    Keywords: Insulin ; glucagon ; somatostatin ; pancreatic exocrine secretion ; chromogranin A ; perfused pancreas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We investigated the effects of porcine pancreastatin on the endocrine and unstimulated exocrine secretion of isolated, perfused porcine pancreas. Pancreastatin in a concentration of 10−8mol/l had no effect on basal secretion of insulin, glucagon and somatostatin at a perfusate glucose concentration of 5 mmol/l (n=4) and neither at 10−8 nor 10−7 mol/l influenced the hormone responses to acute elevations of perfusate glucose concentration from 3.5 to 11 mmol/l (n=7). This elevation strongly stimulated insulin secretion and inhibited glucagon secretion. Exocrine secretion was not affected by pancreastatin. The results suggest that pancreastatin does not directly influence pancreatic secretion.
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  • 81
    ISSN: 1432-1335
    Keywords: Antineoplastic efficacy ; Melphalan ; Diazoxide ; Insulin ; Mammary carcinoma ; Sprague-Dawley rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The anticancer activity of melphalan andN-(2-chloroethyl)-N-nitrosocarbamoyl-ω-lysine (CNC-ω-Lys), was compared in the autochthonous, methylnitrosourea-induced mammary carcinoma of the Sprague-Dawley rat. In addition, the influence on the therapeutic efficacy of the combination with diazoxide, causing a mild, reversible diabetes, and with insulin was investigated. The comparison of melphalan and CNC-ω-Lys clearly showed the superiority of melphalan. Both compounds displayed a significant tumour inhibition in their medium and the highest dosages in comparison to the untreated control. The combination with diazoxide resulted for almost all groups in an increased tumour inhibition. Only the lowest dose of CNC-ω-Lys + diazoxide did not reduce the tumour volume significantly versus the control group. The combination with insulin, however, resulted in a loss of tumour inhibition compared to the effect of the cytotoxic drug alone, although in these groups, too, a significant decrease of tumour volumes versus controls could be observed. Mortality was within tolerable limits (〈20%) through the treatment period for all experimental groups. Median lifespans were increased in all therapy groups, but no additional benefit could be observed in the combination treatment groups.
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  • 82
    ISSN: 1432-1106
    Keywords: Ischemia ; Hypoglycemia ; Calcium transient ; Insulin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The primary objective of this study was to explore why preischemic hypoglycemia, which restricts tissue acidosis during the ischemic insult, does not ameliorate cell damage incurred as a result of transient ischemia. The question arose whether hypoglycemia (plasma glucose concentration 2–3 mM) delays resumption of extrusion of Ca2+ from cells during recirculation. Measurements of extracellular Ca2+ concentration during forebrain ischemia of 15 min duration proved that this was the case. Thus, normoglycemic animals resumed Ca2+ extrusion upon recirculation after a delay of 1.5–2.0 min, and hypoglycemic ones after an additional delay which could amount to 3–4 min. We attempted to explore the cause of this delay. At first sight, the results suggested that resumption of oxidative phosphorylation upon recirculation was substrate limited. However, glucose infusion during ischemia or just after recirculation failed to accelerate Ca2+ extrusion from the cells. A comparison between non-injected and insulin-injected animals at equal plasma glucose concentrations suggested that insulin was responsible for the delay. On analysis, the delay proved to be related to a sluggish recovery of cerebral blood flow. The results suggest that when cell damage is evaluated after transient ischemia in hypo- and normoglycemic subjects, attention should be directed to the period of cell calcium ‘overload’. Unobserved differences in the duration of the calcium transient may also confound interpretation of data on the effects of insulin.
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  • 83
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    European journal of clinical pharmacology 38 (1990), S. 393-395 
    ISSN: 1432-1041
    Keywords: Insulin ; propranolol ; sympathetic stimulus ; heart rate increase ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acute hyperinsulinaemia in the absence of changes in blood glucose increases heart rate in man. Animal studies have suggested that beta-adrenergic blockade does not prevent the insulin-induced increase in heart rate. The aim of the present study was to investigate the acute effect of insulin on heart rate and blood pressure in non diabetic subjects and, in particular, to determine whether beta-adrenergic receptor blockade would significantly influence the effect. On separate days 9 healthy young volunteers were pretreated with either 80 mg propranolol or placebo p.o. After a 60–90 min period of heart rate and blood pressure stabilization, a placebo injection was given intravenously and heart rate and blood pressure were then monitored every 5 min. After 30 min insulin Actrapid MC 0.2 IU/kg body weight was given i.v. A 20% glucose infusion was given to maintain blood glucose at its fasting level. After insulin administration, a rapid and statistically significant increase in heart rate was observed when the patients were pretreated with placebo; pretreatment with propranolol completely prevented this effect. Serum insulin levels were significantly higher than baseline at all times and there was no significant change in blood glucose. The results are consistent with the hypothesis that the insulin-induced increase in heart rate in man may result from stimulation of cardiac sympathetic activity.
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  • 84
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    Pflügers Archiv 415 (1990), S. 494-496 
    ISSN: 1432-2013
    Keywords: Insulin ; a-Wave ; ERG ; Retina ; Na pump
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The reduction in amplitude of the a-wave of the frog ERGs in response to light at seven different intensities recorded from isolated frog retinas (Rana catesbiana) caused by ouabain (10±5 M) was partially prevented dose-dependently by the insulin pre-treatment (between 6.6×10±8 and 6.6×10±5 M). Inversely, however, the already suppressed a-waves by ouabain could not be recovered by the application of insulin. The preventive effect of insulin pretreatment was also significantly dependent upon the stimulus intensity, but not upon the presence of glucose in the external media. The effect of insulin itself on the amplitude of the a-wave was below significance level over the range of its concentrations employed in the present experiments. It was suggested that this effect of insulin on the a-wave can be explained by assuming that insulin enhanced the Na-K pump activity under its suppressed conditions in visual cell.
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  • 85
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    The protein journal 9 (1990), S. 229-233 
    ISSN: 1573-4943
    Keywords: Insulin ; insulin receptor ; binding site ; synthetic peptides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Seven regions of the α subunit of human insulin receptor (HIR) were synthesized and examined for their ability to bind radioiodinated insulin. A peptide representing one of these regions (namely, residues α655–670) exhibited a specific binding activity for insulin. In quantitative radiometric titrations, the binding curves of125I-labeled insulin to adsorbents of peptide α655–670 and of purified placental membrane were similar or superimposable. The binding of radioiodinated insulin to peptide or to membrane adsorbents was completely inhibited by unlabeled insulin, and the inhibition curves indicated that the peptide and the membrane on the adsorbents had similar affinities. Synthetic peptides that were shorter (peptide α661–670) or longer (peptide α651–670) than the region α655–670 exhibited lower insulin-binding activity. It was concluded that an insulin-binding region in the HIR α subunit resides within residues α655–670. The results do not rule out the possibility that other regions of the α subunit may also participate in binding of HIR to insulin, with the region described here forming a “face” within a larger binding site.
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  • 86
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    Protoplasma 159 (1990), S. 118-128 
    ISSN: 1615-6102
    Keywords: Human milk ; Glucose ; Insulin ; Glucose transport ; Mammary gland
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The concentration of glucose in human milk, [Glucose]milk, was directly related to the volume of milk secreted not only during lactogenesis and weaning but also during full lactation. To investigate the mechanism for this observation we first established that glucose equilibrates across the apical membrane of the mammary alveolar cell, using infusion of stable isotopically labelled glucose into lactating women. Our results indicate that [Glucose]milk can be used to measure the glucose concentration in the mammary alveolar cell, [Glucose]cell. We then investigated the regulation of glucose transport into the mammary alveolar cell using glucose clamp methodology in fully lactating and weaning women. Maintenance of high plasma insulin concentrations for four hours under euglycemic conditions had no effect on [Glucose]milk, demonstrating that insulin does not regulate glucose transport into the mammary gland. On the other hand, maintaining the [Glucose]plasma at twice the fasting level resulted in a 3-fold increase in the steady state [Glucose]milk in fully lactating women and a 5-fold increase in [Glucose]milk in weaning women. Kinetic analysis of the data showed that the Vmax for glucose transport into the mammary alveolar cell across the basolateral membrane is regulated by the level of synthetic activity in the mammary alveolar cell.
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  • 87
    ISSN: 1432-0428
    Keywords: Insulin ; epinephrine ; lipolysis ; glucose metabolism ; fat cell ; adipose tissue ; plasma NEFA ; KK ; yellow KK ; C57BL ; diabetes ; genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Adipose tissue of KK mice was less sensitive to insulin in its stimulatory action on glucose oxidation or its inhibitory action on lipolysis, and to epinephrine in its stimulatory action on lipolysis as compared to that of C57BL mice. A lack of appreciable increase in plasma NEFA in response to fasting of the KK mice might be caused by the impaired response of lipolysis to the hormones. — Adipose tissue of KK mice was also less sensitive to insulin-like action of concanavalin A, ouabaine or omission of K+ in the medium on glucose oxidation or lipolysis. Lipolysis in response to theophylline and/or DcAMP was less marked in the tissue of KK mice. The mean diameter of the adipocytes was larger in KK than in C57BL mice. In the experiments using adipocytes with the same diameter, however, the cells of KK mice were less sensitive to the hormones than those of C57BL. — With respect to tissue sensitivity to the hormones, the mean diameter of adipocytes and the response of plasma NEFA to fasting, the F1-hybrid mice of KK and C57BL showed values between those of the parental strains. Yellow hybrid (genetically obese F1-hybrid) mice showed higher sensitivity to insulin in the adipose tissue, more remarkable response of plasma NEFA to fasting as compared with KK mice, although hypertrophy of adipocytes was more pronounced in the yellow hybrid mice. — These findings suggest that insulin insensitivity is associated with epinephrine insensitivity in adipocytes of KK mice; both appear to be subjected to genetic factor(s)per se rather than hypertrophy of the adipocytes. Furthermore, insensitivity to both hormones in the KK mice appears to be caused by a common defect in cellular process other than the hormone receptor systems. These genetically determined abnormalities of adipocytes may result in fat-storage metabolism through hyperinsulinemia; this is very similar to the metabolic profile due to thrifty genotype in human diabetes as proposed by Neel.
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  • 88
    ISSN: 1432-2013
    Keywords: Active Sodium Transport ; Insulin ; Aldosterone ; Vasopressin ; Ouabain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Exposure of either the isolated urinary bladder or abdominal skin ofBufo marinus to the cardiac glycoside ouabain was regularly followed by reversible decreases of electrical potential difference and short-circuit current. Residual sodium-transporting activity, stable after 1–2h, was a function of the concentration of the glycoside. 2. Ouabain-inhibited preparations still reacted to vasopressin: the hormonal effect was decreased in amplitude only, and this in proportion to decrease in baseline activity; a similar observation was made when aldosterone was responsible for hormonal stimulation. 3. On the other hand, the insulin-induced increment in sodium transport was quite sensitive to ouabain inhibition so that this hormonal effect could be eliminated at moderate concentrations of the glycoside; the same held true when sodium transport was stimulated by addition of glucose to substrate-depleted preparations, especially when they were under the influence of aldosterone. 4. The persistence of residual hormonal effects in the presence of ouabain is interpreted as a type of response due to the stimuli (vasopressin, aldosterone in the absence of exogenous substrate) influencing a step distinct from, and probably proximal to, the ouabain-sensitive sodium “pump” mechanism proper. As for the increased ouabain effect noted on preparations stimulated by insulin or by glucose repletion, it suggests another type of response, possibly characterized by a facilitated interaction between ouabain and specific cell membrane ATP-ase set in operation as a consequence of these treatments.
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  • 89
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    Pflügers Archiv 348 (1974), S. 333-342 
    ISSN: 1432-2013
    Keywords: Mouse Pancreas ; Amylase ; Glucose ; Insulin ; Glucagon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glucose inhibited amylase release from batch-incubated and perifused pieces of mouse pancreas. Insulin (100μg/ml) reduced the amylase secretion. These effects, however, seemed to be independent of each other, since diazoxide, a potent inhibitor of glucose-induced insulin release, did not abolish the effect of glucose on amylase secretion. Glucagon (10–100 μg/ml) had no effect on the release of amylase from incubated pancreas. Glucagon has previously been shown to inhibit exocrine secretionin vivo. The present results suggest that the inhibitory action of glucagon may be mediated via an increased level of serum glucose and the subsequent release of insulin.
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  • 90
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    European journal of pediatrics 117 (1974), S. 63-72 
    ISSN: 1432-1076
    Keywords: Growth hormone ; Newborn ; Glucose load ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intravenous glucose tests (0.5 g/kg body weight) were performed in 13 newborn infants during their first 3 days of life. The variations in blood glucose, insulin and GH values were studied. In all patients there was a rise in plasma insulin. The correlation between initial insulin rise and glucose assimilation constant was 0.503 which is almost significant. The glucose load provoked a very variable response in plasma GH concentration, some infants showed a rise, others a fall. If the newborns were grouped according to this reaction it appeared that the GH response could be explained using Wilder's law of initial value. This hypothesis, however, did not stand up to a thorough statistical analysis including a discussion of a less well-known statistical error. In contrast to insulin secretion, GH apparently plays no major role in the short term regulation of the blood sugar in the newborn.
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  • 91
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    European journal of applied physiology 33 (1974), S. 215-226 
    ISSN: 1439-6327
    Keywords: Exercise ; Training ; FFA ; Ketones ; Insulin ; Growth Hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Eight young men underwent a programme of training by running for 30 min at moderate speed three times a week for 4 weeks. Metabolic and hormonal changes in blood were studied during and after a run of 60 min at comparable speeds before and at the end of the training programme. Increases in lactate, pyruvate and plasma FFA during exercise were less after training. Increases in glucose were greater. There was a smaller increase in the post-exercise concentration of blood ketone-bodies after training. Plasma levels of insulin and human growth hormone (HGH) were lower after training. The fall in insulin and the rise in HGH during exercise were also smaller. There is a dissociation of the normal relationship between blood glucose and insulin during exercise. Insulin appears to be more important in the control of fat metabolism, in which its role may be altered by physical training. The changes observed in the longitudinal study of training imply that differences observed in cross-sectional studies of athletes and untrained subjects are not the result of an innate difference but do depend upon metabolic changes related to athletic training.
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  • 92
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    Calcified tissue international 12 (1973), S. 8-15 
    ISSN: 1432-0827
    Keywords: Insulin ; Bone ; Calcium ; Resorption ; Orthophosphate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé L'administration d'insuline cristallisée à des rats thyroparathyroidectomisés provoque une augmentation de la calcémie et de la phosphorémie. Le calcium plasmatique s'élève de façon linéaire entre 31 et 250 m Unités d'insuline/100 g de poids corporel. La courbe obtenue n'est guère différente de celle obtenue par extrait parathyroidien. L'administration simultanée d'insuline et d'extrait parathyroidien à des rats thyro-parathyroidectomisés agit sur la calcémie et la phosphorémie par un effet additif. Lorsque des os frontaux d'embryons de poulet sont cultivésin vitro en présence d'insuline cristallisée, le taux de résorption augmente. L'insuline augmente le taux de consommation en glucose des explants et induit une accumulation de citrate dans le milieu de culture. L'insuline stimule donc la résorption osseuse.
    Abstract: Zusammenfassung Der Plasmagehalt an Calcium und Phosphor bei thyroparathyreoidektomierten Ratten wurde durch die Verabreichung von kristallinem Insulin erhöht. Das Plasmacalcium verhielt sich zwischen 31 und 250 m Einheiten Insulin pro 100 g Körpergewicht linear. Die Steigung der erhaltenen Kurve ist nicht signifikant verschieden von derjenigen, die nach Parathyreoidea-Extrakt erhalten wird. Die gleichzeitige Verabreichung von Insulin und Parathyreoidea-Extrakt von thyroparathyreoidektomierten Ratten hatte eine kumulative Wirkung auf den Gehalt von Calcium und Phosphor im Plasma. Wenn Stirnbeine von Kükenembryos mit kristallinem Insulinin vitro kultiviert wurden, erhöhte sich die Resorptionsrate. Das Insulin steigerte den Glucoseverbrauch der Explantate und verursachte eine Anreicherung von Citrat im Kulturmedium. Die Ergebnisse deuten auf eine Stimulation der Knochenresorption durch Insulin.
    Notes: Abstract the administration of crystalline insulin to thyroparathyroidectomized rats raised their calcium and phosphorus plasma levels. The plasma calcium gave a linear response between 31 and 250 mU of insulin/100 g body weight. The slope obtained is not significantly different from that obtained with parathyroid extract. The simultaneous administration of insulin and parathyroid extract to thyroparathyroidectomized rats affected the calcium and phosphorus plasma levels in an additive fashion. When chick embryo frontal bones were cultivatedin vitro with crystalline insulin the rate of resorption increased. Insulin increased the rate of glucose consumption by the explants and induced the accumulation of citrate in the culture medium. It is concluded that insulin stimulates bone resorption.
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  • 93
    ISSN: 1433-8580
    Keywords: Insulin ; Intestinal hormones ; Atropine ; Vagus ; Insulin ; Intestinale Hormone ; Atropin ; Vagus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung und Schluβfolgerung Bei 35 stoffwechselgesunden freiwilligen Probanden wurde vor sowie nach Atropingabe die Wirkung der intestinalen Hormone Sekretin und Cholecystokinin-Pankreozymin (CCK-PZ) auf die endokrine und exokrine Pankreasfunktion untersucht. Außerdem wurde die Wirkung von intravenös und oral bzw. intraduodenal verabreichter Glucose und Aminosäuren auf die Insulinsekretion, den Blutzucker und die freien Fettsäuren ebenfalls vor und nach Atropinmedikation geprüft. Intravenös verabreichtes Sekretin konnte weder in seiner exokrinen noch endokrinen Pankreasfunktion durch Atropin beeinflußt werden. Intravenös injiziertes CCK-PZ konnte mittels Atropin sowohl in seiner ekbolischen wie auch endokrinen Pankreasfunktion gehemmt werden. Die Wirkung von CCK-PZ ist somit an ein cholinerges System gebunden, so daß es erlaubt erscheint, bezüglich der Pankreozyminwirkung von einem synergistisch bzw. additiv wirksam werdenden „neurohormonalen“ Mechanismus zu sprechen. Die durch parenteral verabreichte Glucose oder Aminosäuren induzierte Insulinsekretion wurde durch Atropin nicht beeinflußt; hingegen hemmte Atropin dieβ-cytotrope Wirkung von oral bzw. intraduodenal verabreichter Glucose oder Aminosäuren. Dies läßt auf eine Abhängigkeit von einem cholinergen oder parasympathischen System in der Freisetzung dieser intestinalen Hormone schließen.
    Notes: Summary and Conclusions In 35 metabolically normal subjects the effect of i.v. secretin and cholecystokinin-pancreozymin (CCK/PZ) on the endocrine and exocrine pancreatic function was investigated, before and after atropine. In addition, the effect of oral, intravenous and intraduodenal administration of glucose and amino acids on blood sugar and free fatty acids before and after the injection of atropine was studied. The secretin stimulated endocrine and exocrine pancreas was not affected by atropine. However, atropine inhibited the ecbolic and endocrine pancreatic function after stimulation with CCK/PZ. Therefore, the effect of i.v. CCK/PZ seems to be mediated by the cholinergic system, or even a “neuro-hormonal” system which acts synergically or additively. No influence of atropine on the insulin secretion induced by i.v. glucose or amino acids was observed. On the other hand, atropine inhibited the beta-cytotropic effect of glucose and amino acids after oral or intraduodenal administration. These findings indicate that the release of these intestinal hormones is dependent on the cholinergic or parasympathetic system.
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  • 94
    ISSN: 1433-8580
    Keywords: Small intestine ; Absorption ; Insulin ; Man ; Dünndarm ; Resorption ; Insulin ; Mensch
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Der Einfluß von Insulin auf die Resorption von Glucose, Wasser, Natrium und Kalium wurde mittels der segmentalen Dünndarmperfusion mit einer dreilumigen Sonde untersucht. Nach Messung der Resorption über zwei 30 min-Perioden wurden den Probanden 1,0 g Tolbutamid (Rastinon®) bzw. 20 IE Insulin (Actrapid®) intravenös injiziert und danach die Resorption über vier 15 min-Perioden bestimmt. Ergebnisse 1. Stoffwechselgesunde zeigten sowohl nach Injektion von Tolbutamid und dadurch induzierter Erhöhung des Seruminsulinspiegels als auch nach Insulininjektion eine signifikante Minderung der Resorption. 2. Diese Resorptionsminderung war auch nachweisbar, wenn Glucose zur Verhinderung des Blutzuckerabfalls unmittelbar nach der Insulininjektion infundiert wurde. 3. Insulinbedürftige Diabetiker lassen nach der Injektion von Tolbutamid — offenbar infolge fehlender Insulinsekretion — keine Resorptionsänderungen erkennen, zeigen aber eine Transportminderung nach Insulininjektion. Diese Befunde belegen, daß die Glucose-, Wasser-, Natrium- und Kaliumresorption im menschlichen Dünndarm durch Insulin reduziert wird.
    Notes: Summary The influence of insulin on the intestinal absorption of glucose, water, sodium and potassium was investigated in man using a triple lumen tube technique. After an absorption period of 60 min 1 g of tolbutamide was injected in order to stimulate endogenous insulin secretion. Alternatively 20 units of regular insulin were applied intravenously. Thereafter absorption was studied over 4 periods of 15 min duration. Results: 1. In healthy subjects the absorption of glucose water, sodium and potassium was decreased after the injection of tolbutamide as well as after the injection of insulin. 2. The decrease in absorption was also demonstrable when the insulin induced reduction of blood sugar levels was abolished by intravenous glucose infusion. 3. In insulin dependent diabetics there was no decrease in absorption after injection of tolbutamide. This was due to the unability to secrete insulin. On the other hand a decrease in absorption occurred if insulin was applied in insulin dependent diabetics. These results demonstrate that the absorption of glucose, water, sodium and potassium from the human intestine is reduced by insulin.
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    Electronic Resource
    Springer
    Diabetologia 9 (1973), S. 447-452 
    ISSN: 1432-0428
    Keywords: Insulin ; obese mice ; pancreas ; glucose ; amino acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pancreatic insulin content and insulin secretion, from the pancreas of obese mice fed ad lib (ob/ob), obese mice maintained on a restricted diet (ob/ob RD) and lean mice has been studied using incubated pieces of pancreas in vitro and in a perifusion system. The ob/ob mice pancreas contained approximately twice as much insulin as the lean mice pancreas, whereas the ob/ob RD mice had a normal insulin content. Increasing the glucose concentration had a marked and prolonged stimulating effect on insulin secretion in the pancreas of the ob/ob and ob/ob RD mouse, but not in the lean mouse. Leucine stimulated insulin secretion in all three groups of animals both in the absence and presence of glucose in a biphasic manner; in the presence of glucose the insulin secreted from the pancreas of the ob/ob and ob/ob RD mice was abnormally high. Arginine stimulated insulin secretion from the lean mouse pancreas in the absence of glucose, whereas in the obese mouse pancreas stimulation was observed only in the presence of glucose, and the effect increased with increasing glucose concentration. The large amounts of insulin which can be secreted by the pancreas of the ob/ob and ob/ob RD mice under stimulation suggest that an abnormal response of the pancreas to biological stimuli of insulin secretion could be a primary defect in these animals.
    Type of Medium: Electronic Resource
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  • 96
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 9 (1973), S. 174-177 
    ISSN: 1432-0428
    Keywords: Insulin ; clearance ; perfusion ; radioimmunoassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hepatic insulin clearance was studied in normal male and female Wistar rats using the isolated liver perfusion technique and the dextran coated charcoal radioimmunoassay for insulin. The following results were obtained: — 1. In male rats there was a progressive increase in clearance with increasing body weight, liver weight and age. — 2. In adult female rats clearance was significantly greater than in comparable males, but no relationship between liver weight and clearance was observed. — 3. With each increase in insulin concentration there was an apparent decrease in clearance.
    Type of Medium: Electronic Resource
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  • 97
    ISSN: 1432-2013
    Keywords: RQ ; Insulin ; Glucose ; Lactate ; Pyruvate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary RQ, plasma insulin, blood glucose, lactate and pyruvate were measured in six fit, normal subjects during a series of exercise and rest experiments with and without sucrose ingestion. Subjects exercised on a bicycle ergometer for 50 min of every hour for 6 h at about 47% of the group's average maximal aerobic capacity. In the resting experiments, the subjects sat for 6 h in an armchair. A solution containing 100 g of sucrose was ingested at the beginning of the fourth hour during the sucrose experiments. Ingestion of sucrose caused a significant increase in RQ, plasma insulin, blood glucose, lactate and pyruvate in both exercise and rest experiments. Insulin, lactate and pyruvate concentrations rose higher during rest after sucrose ingestion than during exercise. The time courses of the changes in RQ, insulin, glucose, lactate and pyruvate after sucrose ingestion, suggest that glucose entering the cell during rest is immediately oxidized, while during work there is some delay in the oxidation of glucose.
    Type of Medium: Electronic Resource
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  • 98
    ISSN: 1432-2013
    Keywords: Insulin ; Muscle Metabolism ; Carbohydrate Metabolism ; “Bis-Phosphoenolpyruvate”
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The time course of the insulin effect on 1,2-bis-phosphoenolpyruvate (bis-PEP), a glucose metabolite, has been investigated. Within 30 sec insulin causes an increase of 60% in the amount of bis-PEP accumulated in incubation media of rat diaphragms.
    Type of Medium: Electronic Resource
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  • 99
    ISSN: 1432-1440
    Keywords: long acting glucagon ; glucose ; free fatty acids ; insulin ; left ventricular contractility ; Depot-Glucagon ; Glucosestoffwechsel ; freie Fettsäuren ; Insulin ; linksventriculäre Kontraktilität
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Zink-Protamin-Glucagon zeigt bei s.c.-Injektion in einer Dosis von 5 mg einen deutlichen, aber protrahierten Anstieg des Blutzuckers um rund 40% innerhalb 1 Std und behält dieses erhöhte Niveau durch mehrere Stunden bei. Die Lipase-Aktivitätssteigerung nach Glucagon ist beim Menschen nur kurzfristig und unbedeutend [rund 7% ige Zunahme der freien Fettsäuren (FFS) 10 min p. inj.], sie wird von einem insulininduzierten Abfall der FFS um rund 50% im Laufe von 6 Std gefolgt. Die Zunahme der Insulinspiegel im Serum ist zwar statistisch signifikant, erreicht aber nicht das Ausmaß der von der intravenösen Verabreichung bekannten Veränderungen. Die hämodynamischen Effekte einer Einzeldosis von 5 mg Zink-Protamin-Glucagon sind nicht eindeutig und lassen lediglich eine nicht signifikante Zunahme von LVdp/dt max um 16,7% nach 15 min erkennen, während alle anderen Parameter im wesentlichen unverändert bleiben. Die mögliche klinische Bedeutung dieser Glucagoneffekte wird diskutiert.
    Notes: Summary The subcutaneous injection of 5 mg of zincprotamine-glucagon results in a 40% increase of blood glucose within 1 hour; this elevated level is maintained for several hours. The activation of lipase after the administration of glucagon in patients is insignificant and of short duration (only 7% rise of plasma FFA 10 minutes after injection) and is followed by an insulin-induced fall of plasma FFA by 50% within 6 hours. There is a concomitant, statistically significant rise in serum insulin. Haemodynamic measurements following a single dose of 5 mg of zinc-protamine-glucagon revealed only a statistically non significant 16.7% rise in LVdp/dt max, after 15 minutes, the other parameters remaining essentially unchanged. The possible elinical significance of these glucagon effects is discussed.
    Type of Medium: Electronic Resource
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  • 100
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 51 (1973), S. 63-67 
    ISSN: 1432-1440
    Keywords: Insulin ; glycaemia ; diabetes ; radioimmunoassay ; Insulin ; Glycaemia ; Diabetes ; Radioimmunoassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Bestimmung des immunoreaktiven Insulins im Plasma hat in der Diagnostik insulinsezernierender Tumoren allgemein Anwendung gefunden. Beim Diabetes mellitus ist diese Untersuchung von großer Bedeutung zur Unterscheidung der metabolischen und pankreatischen Faktoren dieser Krankheit. Sie erleichtert sowohl die Entscheidung in der Wahl der Therapie als auch die weitere Verlaufskontrolle.
    Notes: Summary The use of the measurement of plasma immunoreactive insulin levels is generally accepted for the diagnosis of insulin-secreting tumours. In diabetes, this determination is of major importance for the differentiation between the metabolic and pancreatic factors involved in the disease and it is helpful both for initiating therapy and following up cases over the years.
    Type of Medium: Electronic Resource
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