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  • 1990-1994  (19)
  • 1985-1989
  • 1965-1969
  • 1920-1924
  • 1994  (19)
  • Insulin
  • 1
    Electronic Resource
    Electronic Resource
    The effect of a ventral medial hypothalamic lesion on the insulin-induced hypotensive response in normal rats (1994)
    Springer
    Acta diabetologica 31 (1994), S. 91-97 
    Details
    ISSN: 1432-5233
    Keywords: Insulin ; VMH ; Cardiovascular response ; VMH lesion ; Blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The cardiovascular responses to insulin-induced hypoglycemia were studied in normal and ventral medial hypothalamic (VMH)-lesioned rats. The goal of this study was to investigate the role of the VMH in mediating the insulin-induced decreases in cardiovascular tone. Male Wistar rats were anesthetized with urethane/chloralose. Following the induction of anesthesia, the trachea, femoral artery, and femoral vein were cannulated. The femoral artery was attached to a pressure transducer for cardiovascular monitoring. The cardiovascular activity was recorded using a Modular Instruments Micro 5000 signal processing system. The mean arterial pressure and pulse pressures and heart rate were evaluated. In control studies, a stable plasma glucose and blood pressure were obtained with urethane/chloralose anesthesia for the duration of the experiments. Insulin (2.0 or 5.0 U/kg) significantly decreased the plasma glucose as well as the blood pressure. In VMH-lesioned rats, the lesions were accomplished by radiofrequency, and the cardiovascular response to insulin-induced hypoglycemia was investigated 1 or 6 weeks later. There was no difference in the cardiovascular response to insulin-induced hypoglycemia between the low or high insulin dose after 1 week in VMH-lesioned animals. The low dose after 6 weeks in VMH-lesioned animals did not produce a change in the mean arterial pressure response compared with controls. The pulse pressure was higher than in the sham-lesioned animals, and the plasma glucose response was greater. The high dose after 6 weeks in VMH-lesioned animals in contrast to sham-lesioned animals led to an increased cardiovascular response instead of a decrease. We propose that the decrease in cardiovascular activity in response to insulin-induced hypoglycemia in normal animals can be attributed to a direct or indirect effect on vascular dilation as well as possibly to an inhibition of sympathetic firing. However, it appears that insulin increases the vascular dilation as well as the parasympathetic tone after 1 week in the VMH-lesioned animals, similar to the findings in sham-lesioned animals. However, after 6 weeks, the insulin-induced decreased cardiovascular tone is minimal. Thus, we believe hat the VMH does not have a direct effect in modulating the insulin-induced decrease in cardiovascular tone, but its destruction appears to influence other regulatory centers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00570542
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  • 2
    Electronic Resource
    Electronic Resource
    Immunocytochemical and ultrastructural heterogeneities of normal and glibenclamide stimulated pancreatic beta cells in the rat (1994)
    Springer
    Virchows Archiv 425 (1994), S. 305-313 
    Details
    ISSN: 1432-2307
    Keywords: Rat ; Pancreatic beta cells ; Immunocytochemistry ; Ultrastructure ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract When studied morphologically in semi-thin sections in the rat in vivo, pancreatic beta cells displayed heterogeneous immunoreactivities for insulin and amylin, depending on the islet size and the intra-islet position of the beta cells. In larger islets, cortical beta cells (beta cells with contacts with all islet cell types and with the exocrine parenchyma) which are located in the periphery were more densely immunostained for insulin and amylin than medullary beta cells (beta cells with contacts only with other beta cells) which are located in the centre of the islet. Ultrastructurally, these findings were accompanied by differences in the number of secretory granules and mitochondria. Beta cells in small islets and at extra-islet sites exhibited a dense immunoreactivity. After administration of glibenclamide, immunoreactivities for insulin and amylin were diminished in a time-dependent manner, decreasing first in medullary and thereafter in cortical beta cells of larger islets. Ultrastructurally, the beta cells exhibited the typical signs of stimulation. A minority of beta cells in small islets and all beta cells in extra-islet locations remained unchanged. Thus pancreatic beta cells under basal and stimulatory conditions in vivo exhibit heterogeneity in hormone content and in ultrastructural features. These differences may represent the basis for a functional heterogeneity of the insulin secretory response of the individual beta cell both in vivo and in vitro in states of normal and impaired insulin secretion. As heterogeneity was observed only among beta cells in islets, while single beta cells surrounded by acinar cells exhibited no changes in insulin immunoreactivity, interactions between beta cells as well as between beta cells and other endocrine cells may be critical for expression of heterogeneity within the beta cell population.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00196154
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  • 3
    Electronic Resource
    Electronic Resource
    Structure-activity relationship of covalently dimerized insulin derivatives: correlation of partial agonist efficacy with cross-linkage at lysine B29 (1994)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 350 (1994), S. 213-217 
    Details
    ISSN: 1432-1912
    Keywords: Insulin ; Dimerized insulin derivatives ; Insulin receptor antagonists ; Glucose transport ; 3T3-L1 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of 7 covalently dimerized insulin derivatives on glucose transport in differentiated 3T3-L1 cells were investigated. Symmetric cross-linkage at lysine B29 with a bridge of 2 (oxalyl), 8 (suberoyl) or 12 (dodecanedioyl) carbon atoms produced derivatives with essentially unaltered receptor binding affinity but largely reduced intrinsic activity. Regardless of the chain length, these derivatives inhibited the effect of submaximal insulin concentrations. Insulin derivatives cross-linked at phenylalanine 131 or asymmetrically at 131/1129 were full agonists of the insulin receptor. When lysine B29 was cross-linked with the inactive desoctapeptide(B23-B30)insulin at phenylalanine B1, the intrinsic activity of the resulting dimer was lower than that of insulin, but higher than that of the symmetric B29-dimers. It is concluded that linkage at the B29-lysines, and not at the B1-phenylalanine, leads to partial agonism of dimerized insulin derivatives, regardless of the length of the crosslinker.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00241099
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  • 4
    Electronic Resource
    Electronic Resource
    Insulin and growth in chronic renal failure (1994)
    Springer
    Pediatric nephrology 8 (1994), S. 309-312 
    Details
    ISSN: 1432-198X
    Keywords: Glucose ; Insulin ; Growth ; Chronic renal failure ; Uremia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied glucose metabolism using the hyperglycemic technique in a cross-section of 23 children (15 pubertal, 8 prepubertal) with stable chronic renal failure as a possible cause of their poor growth. Linear growth was expressed as growth velocity standard deviation score (GVSDS). GVSDS correlated with glucose disposal rate but not with insulin sensitivity index in the pubertal (r=0.87,P〈0.001) and prepubertal (r=0.86,P〈0.02) children with chronic renal failure. Thirteen children were followed longitudinally during medical suppression of hyperparathyroidism with dietary phosphate restriction and high-dose phosphate binders. Following significant suppression of serum parathyroid hormone (PTH) levels back to the normal range (932±240 ng/l to 199±50 ng/l), GVSDS, glucose disposal rate and insulin secretion all increased significantly (P〈0.01), with no change in insulin sensitivity index and renal function. The changes in GVSDS correlated with the changes in glucose disposal rate (r=0.86,P〈0.02) and with the changes in insulin secretion (r=0.80,P〈0.01). However, the changes in GVSDS did not correlate with the changes in PTH. The hypothesis that insulin may be more important than PTH in the pathogenesis of growth failure in chronic renal disease deserves further investigation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00866344
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  • 5
    Electronic Resource
    Electronic Resource
    Study on growth hormone and insulin secretion in myotonic dystrophy (1994)
    Springer
    Journal of molecular medicine 72 (1994), S. 508-511 
    Details
    ISSN: 1432-1440
    Keywords: Myotonic dystrophy ; Growth hormone ; Growth hormone releasing hormone ; Insulin ; C-Peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Growth hormone (GH) levels were measured in 12 patients with myotonic dystrophy (MD; 7 men and 5 women, aged 21–49 years) and 14 volunteers after administration of 100 μg GH-releasing hormone (GHRH; 1–29). A 75-g oral glucose tolerance test was carried out to determine glucose, insulin, plasma C-peptide, and urinary C-peptide. The GH level in six MD patients responded normally to GHRH (group I), with a peak of 17.1 ± 1.46 μg/l, compared withcontrols (27.8 ± 19.6 μg/l, NS), and that in the other six patients responded subnormally, with a peak of 3.15 ± 1.46 μg/l, lower than in controls and in group I patients (P 〈 0.001). In group I the insulin response to the glucose tolerance test showed hyperinsulinism and was lower than that in group II patients; stimulated C-peptide was also higher in group II than in group I and in controls; urinary C-peptide levels were parallel to those in previous data. In all MD patients there were a negative correlation between absolute values of GH response to GHRH and insulin response to glucose tolerance test (r = - 0.79, P 〈 0.001). Our data suggest that the failure in GH release and peripheral insulin action is due to a generalized defect in cellular membrane function in MD patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00207479
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  • 6
    Electronic Resource
    Electronic Resource
    Differential effects of insulin and insulin-like growth factor-I in the femoral tissues of rats with skeletal unloading (1994)
    Springer
    Calcified tissue international 55 (1994), S. 363-367 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00299316
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  • 7
    Electronic Resource
    Electronic Resource
    Effect of metformin on insulin-stimulated glucose transport in isolated skeletal muscle obtained from patients with NIDDM (1994)
    Springer
    Diabetologia 37 (1994), S. 826-832 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00404340
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  • 8
    Electronic Resource
    Electronic Resource
    Comparative studies on the dynamics of crosslinked insulin (1994)
    Springer
    European biophysics journal 23 (1994), S. 177-187 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01007609
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  • 9
    Electronic Resource
    Electronic Resource
    Painfulness of needle and jet injection in children with diabetes mellitus (1994)
    Springer
    European journal of pediatrics 153 (1994), S. 409-410 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01983402
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  • 10
    Electronic Resource
    Electronic Resource
    Assessment of the labelling index of cohorts of the pancreatic islet cell population in phenobarbitone-treated male rats using a double immunohistochemical technique for 5-bromo-2′-deoxyuridine and pancreatic hormones (1994)
    Springer
    Archives of toxicology 69 (1994), S. 52-58 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050137
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  • 11
    Electronic Resource
    Electronic Resource
    Transgenic mice overproducing islet amyloid polypeptide have increased insulin storage and secretion in vitro (1994)
    Springer
    Diabetologia 37 (1994), S. 725-728 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00417699
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  • 12
    Electronic Resource
    Electronic Resource
    Differences in umbilical cord insulin and birth weight in non-diabetic pregnancies of women from different ethnic groups in New Zealand (1994)
    Springer
    Diabetologia 37 (1994), S. 930-936 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400950
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  • 13
    Electronic Resource
    Electronic Resource
    Glucose kinetics during prolonged exercise in euglycaemic and hyperglycaemic subjects (1994)
    Springer
    Pflügers Archiv 426 (1994), S. 378-386 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00388300
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  • 14
    Electronic Resource
    Electronic Resource
    Effect of systemic insulin on protein kinetics in postoperative cancer patients (1994)
    Springer
    Annals of surgical oncology 1 (1994), S. 321-328 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02303571
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  • 15
    Electronic Resource
    Electronic Resource
    Insulin synthesis in chick embryo retinas during development (1994)
    Springer
    Neurochemical research 19 (1994), S. 821-825 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00967450
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  • 16
    Electronic Resource
    Electronic Resource
    Hypoxia and training-induced adaptation of hormonal responses to exercise in humans (1994)
    Springer
    European journal of applied physiology 68 (1994), S. 303-309 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00571448
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  • 17
    Electronic Resource
    Electronic Resource
    Insulin family growth factors have specific effects on protein synthesis in preimplantation mouse embryos (1994)
    New York, NY [u.a.] : Wiley-Blackwell
    Molecular Reproduction and Development 37 (1994), S. 398-406 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/mrd.1080370406
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  • 18
    Electronic Resource
    Electronic Resource
    Morphological effects of diabetes on the granular ducts and acini of the rat submandibular gland (1994)
    New York, NY [u.a.] : Wiley-Blackwell
    Microscopy Research and Technique 27 (1994), S. 61-70 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jemt.1070270105
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  • 19
    Electronic Resource
    Electronic Resource
    Tissue insulin contents in nesidioblastosis. Report of two cases (1994)
    Springer
    Pediatric surgery international 9 (1994), S. 353-356 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01685999
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