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  • 1
    Electronic Resource
    Electronic Resource
    Glucoreceptor mechanisms and the control of insulin release and biosynthesis (1980)
    Springer
    Diabetologia 18 (1980), S. 5-15 
    Details
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The models proposed for the means whereby the B-cell recognises glucose and related compounds as signals for insulin release and biosynthesis are discussed. The observed correlations between rates of metabolism and insulin release and biosynthesis are consistent with the substrate-site hypothesis. For glucose itself, the enzymes catalysing the phosphorylation of the sugar provide an explanation for the major characteristics of the islet responses, but for N-acetylglucosamine evidence is presented that the sugar transport system fulfils this discriminatory role. Possible mechanisms whereby sugar metabolism may be linked to changes in Ca2+-handling are considered and evidence is given supporting a role for the cytosolic NADPH/NADP+ ratio and the islet content of phosphoenolpyruvate. The nature of the targets for cyclic AMP and Ca2+ is discussed and some properties of islet cAMP-dependent protein kinase are summarised. Evidence is presented for the presence of calmodulin in islets and the possible involvement of calmodulin in stimulussecretion coupling. On the basis of these considerations a speculative hypothesis for the mechanisms involved in the B-cell responses to glucose is out lined.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01228295
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  • 2
    Electronic Resource
    Electronic Resource
    Effects of an enkephalin analogue (DAMME) on insulin release from cultured rat islets of langerhans (1981)
    Springer
    Diabetologia 20 (1981), S. 642-646 
    Details
    ISSN: 1432-0428
    Keywords: Enkephalin ; insulin secretion ; islets of Langerhans ; naloxone ; islet culture ; DAMME
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rat islets of Langerhans were maintained for 2 days in tissue culture. Following the culture period, the insulin secretory responses of the islets on incubation in bicarbonate medium were measured. The enkephalin analogue D-ala2, MePhe4, Met(0)-ol (DAMME), 8.3×10-8mol/l, augmented insulin release stimulated by glucose (5 or 7 mmol/l) by 76% and 47% respectively; increased insulin release stimulated by α-ketoisocaproate (7.5 mmol/l) by 23%; and enhanced insulin release in the presence of glibenclamide (10 μg/ml) plus glucose (3.3 mmol/l) by 38%. Insulin release in the presence of glucose at 2 or 12 mmol/l was not affected by DAMME (8.3×10-8mol/l). The potentiatory effect of DAMME on insulin release in the presence of glucose (5 mmol/l) was blocked by naloxone (11 μmol/l): naloxone alone did not affect glucose-stimulated insulin release. A high concentration (3.3×10-6mol/l) of DAMME did not modify glucose-stimulated insulin release. Inhibition of glucose-stimulated insulin release by trifluoperazine, an inhibitor of calmodulin, was not overcome by DAMME. Insulin secretory responses were not enhanced by exposure of the islets to DAMME (8.3×10-8mol/l) during the culture period. It is concluded that insulin release from isolated islets is capable of being influenced by an opioid peptide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00257434
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  • 3
    Electronic Resource
    Electronic Resource
    Insulin release from human pancreatic islets in vitro (1980)
    Springer
    Diabetologia 19 (1980), S. 114-117 
    Details
    ISSN: 1432-0428
    Keywords: Insulin secretion ; human islets of Langerhans ; pancreatic β-cell ; tissue culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Islets of Langerhans were isolated by collagenase digestion from the pancreas of a 39 year-old female renal transplant donor. The islets were subjected to three consecutive periods of tissue culture, after each of which they were incubated in vitro with various agents whose effects on insulin release from islets of laboratory animals have previously been established. After the first culture period, the basal insulin secretion rate of 5.2 μU/islet/h seen with 2 mmol/l glucose was increased approx. 5-fold on raising the glucose concentration to 20 mmol/l. The islets retained the insulin-secretory response to 20 mmol/l glucose throughout the period of study. Insulin secretion was also stimulated by mannose, leucine, α-ketoisocaproate, dihydroxyacetone and 3-hydroxybutyrate, but not by fructose or N-acetyl-glucosamine. Fructose however increased insulin release in the presence of 4 mmol/l glucose. Caffeine elicited insulin release in the absence of glucose and enhanced insulin release in response to 10 mmol/l glucose. Glucose-stimulated insulin release was inhibited by trifluoperazine (25 μmol/l).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00421856
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  • 4
    Electronic Resource
    Electronic Resource
    Effects of hypophysectomy and growth hormone on cultured islets of Langerhans of the rat (1982)
    Springer
    Diabetologia 22 (1982), S. 134-137 
    Details
    ISSN: 1432-0428
    Keywords: Insulin release ; insulin biosynthesis ; growth hormone ; calmodulin ; cyclic AMP ; islet glucose metabolism ; hypophysectomy ; cultured islets
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects on islet function of addition to the culture medium of rat growth hormone was studied in 4-day cultured islets of Langerhans from normal and hypophysectomised rats. In islets from hypophysectomised rats, rates of insulin release were 34% lower than in control rat islets; rates of insulin plus proinsulin and total protein biosynthesis were also lower by 48% and 16% respectively. The rates of glucose oxidation and the islet content of cyclic AMP were unchanged in islets from hypophysectomised rats but the islet content of calmodulin was decreased by 68%. The presence of rat growth hormone during the culture period restored the secretory response of hypophysectomised rat islets to that seen in control islets cultured without growth hormone but had only a marginal effect on the rate of insulin plus proinsulin biosynthesis, and no significant effect on islet calmodulin content. Glucose oxidation was increased by the presence of growth hormone during the culture period in both control (73% increase) and hypophysectomised (38% increase) rat islets. Addition of growth hormone to the culture medium also enhanced rates of insulin release and biosynthesis in control islets by 116% and 20% respectively. It is suggested that these changes arise primarily from modification of the synthesis of specific islet proteins.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00254843
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  • 5
    Electronic Resource
    Electronic Resource
    Phosphoenolpyruvate in rat pancreatic islets: A possible intracellular trigger of insulin release? (1977)
    Springer
    Diabetologia 13 (1977), S. 481-486 
    Details
    ISSN: 1432-0428
    Keywords: Islets of Langerhans ; insulin ; glucose ; glyceraldehyde ; phosphoenolpyruvate ; glucoreceptor ; substrate-site ; regulator-site ; pyruvate kinase ; mannoheptulose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The content of phosphoenolpyruvate (PEP) has been measured in isolated rat islets of Langerhans incubated in vitro. Islet PEP was higher in islets incubated with 16.7 mmol/l glucose than in islets incubated with zero or 2.8 mmol/l glucose. Islet PEP content was also increased in islets incubated with 5 mmol/l D-glyceraldehyde. Mannoheptulose abolished the glucose-induced rise in PEP content but not that elicited by D-glyceraldehyde. These results are consistent with a role for PEP as an intracellular mediator of glucose- and glyceraldehyde-induced insulin release. The kinetics of pyruvate kinase in extracts of rat islets were studied. The maximal extractable activity was considerably higher than known rates of glycolytic flux. The Km values were found to be 0.16 mmol/l for PEP and 0.5 mmol/l for ADP. The control of islet PEP content and the possible role of PEP in insulin release are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01234500
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  • 6
    Electronic Resource
    Electronic Resource
    The effects of glucose, N-acetylglucosamine, glyceraldehyde and other sugars on insulin release in vivo (1975)
    Springer
    Diabetologia 11 (1975), S. 279-284 
    Details
    ISSN: 1432-0428
    Keywords: N-acetylglucosamine ; insulin release ; glyceraldehyde ; glucose ; glucosamine ; fructose ; galactose ; mannoheptulose ; glucoreceptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The specificity for carbohydrates of insulin secretory responses in vivo was studied. Test sugars were injected via a left femoral vein cannula into conscious rats. Blood samples collected over the ensuing 60 min via a left femoral arterial cannula were assayed for plasma insulin and glucose, and, in some experiments, for N-acetyl glucosamine. Whereas L-glucose or saline produced no significant changes in plasma insulin or glucose concentrations, D-glucose, N-acetylglucosamine, D-glucosamine, fructose, D-glyceraldehyde and DL-glyceraldehyde were potent secretagogues. Simultaneous injection of mannoheptulose abolished the insulin-otropic action of glucose and N-acetylglucosamine, but not of DL-glyceraldehyde. Fructose, glucosamine, and DL-glyceraldehyde induced hyperglycaemia, but peak insulin concentrations occurred before any change in plasma glucose concentration. No evidence was obtained for a stimulatory effect of galactose on insulin release. Infusion for 60 min of N-acetylglucosamine produced a sustained elevated plasma insulin concentration and significant hypoglycaemia. The present in vivo results agree with previous in vitro observations, and could indicate a role for sugars other than glucose in the regulation of insulin release.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00422392
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  • 7
    Electronic Resource
    Electronic Resource
    Effects of phosphoenolpyruvate, other glycolytic intermediates and methylxanthines on calcium uptake by a mitochondrial fraction from rat pancreatic islets (1978)
    Springer
    Diabetologia 15 (1978), S. 173-180 
    Details
    ISSN: 1432-0428
    Keywords: Islets of Langerhans ; insulin ; glucose ; phosphoenolpyruvate ; substrate-site ; methylxanthines ; cyclic AMP ; calcium ; mitochondria ; fructose 1,6-diphosphate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 45Ca2+-accumulation by a mitochondrial fraction from isolated rat pancreatic islets was strongly stimulated by ATP. The ATP-dependent uptake was inhibited by phosphoenolpyruvate in a dose-dependent manner over a wide variety of conditions. Inhibition by phosphoenolpyruvate was noncompetitive with respect to calcium, competitive with respect to magnesium, and antagonised by high Mg-ATP2− concentrations; fructose 1,6-diphosphate also decreased 45Ca2+-uptake. Other glucose metabolites were either less effective or ineffective in diminishing mitochondrial 45Ca2+-accumulation. The ATP-dependent uptake was also inhibited by xanthine derivatives (caffeine and 3-isobutyl-l-methylxanthine) which potentiate the effects of glucose on insulin secretion. Cyclic AMP had no effect. It is thought that the rate of insulin secretion is a function of the cytosolic calcium concentration in the B-cell. These data show that phosphoenolpyruvate, fructose 1,6-diphosphate and methylxanthines might influence exocytosis by direct effects on mitochondrial calcium accumulation, and thus the intracellular distribution of calcium.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00421235
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  • 8
    Electronic Resource
    Electronic Resource
    β-Cell recognition of stereoisomers of D-glucose (1979)
    Springer
    Diabetologia 17 (1979), S. 165-168 
    Details
    ISSN: 1432-0428
    Keywords: Insulin release ; insulin biosynthesis ; islet lactate output ; glucoreceptor ; D-aldohexose stereoisomers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ability of all eight D-aldohexose steroisomers to stimulate insulin release and biosynthesis was compared with their ability to serve as a metabolic substrate for isolated islets of Langerhans as judged by formation of lactate. Insulin release and synthesis were stimulated by glucose or mannose but not by allose, altrose, gulose, idose, galactose or talose. No potentiary effects of allose, altrose, gulose, idose, or talose were found on insulin release in the presence of 4 mmol/l glucose nor did these sugars inhibit insulin release in the presence of 20 mmol/l glucose. Lactate formation was increased above values found in the absence of added substrate by 20 mmol/l D-glucose or mannose, but not by allose, altrose, gulose, galactose or talose. The results support ]the substrate-site hypothesis for the recognition of sugars as stimuli of insulin release and synthesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01219744
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  • 9
    Electronic Resource
    Electronic Resource
    Effects of growth hormone on insulin release in the rat (1980)
    Springer
    Diabetologia 19 (1980), S. 391-396 
    Details
    ISSN: 1432-0428
    Keywords: Growth hormone ; hypophysectomy ; plasma growth hormone ; plasma insulin, insulin release ; perifusion ; cultured rat islets
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Growth hormone injected intravenously in the rat elicited a 6-fold spike change in immunoreactive insulin with little variation in glucose. Subcutaneous administration of growth hormone for 4 days augmented by 56% the insulin-secretory response to glucose of isolated islets from hypophysectomised rats but not the response of control rat islets. When islets were cultured in the presence of growth hormone, the glucose-induced insulin release was increased by 35% in batch incubations of islets from both normal and hypophysectomised rats and by 70–110% in perifused islets. Thus the capacity for stimulated release of insulin is limited by hypophysectomy, and growth hormone is capable of directly influencing the secretory function of the β- cell.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280526
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  • 10
    Electronic Resource
    Electronic Resource
    Erratum (1982)
    Springer
    Diabetologia 22 (1982), S. 300-300 
    Details
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00281314
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