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  • Articles: DFG German National Licenses  (8)
  • insulin secretion  (6)
  • substrate-site  (2)
  • 1
    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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  • 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
    Diabetogenic action of alloxan-like compounds: The effect of dehydrouramil hydrate hydrochloride on isolated islets of langerhans of the rat (1983)
    Springer
    Diabetologia 25 (1983), S. 360-364 
    Details
    ISSN: 1432-0428
    Keywords: Dehydrouramil hydrate hydrochloride ; alloxan ; diabetes ; islets of Langerhans ; insulin secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Dehydrouramil hydrate hydrochloride (DHU) is an analogue of alloxan which retains the in vivo diabetogenic activity of alloxan but, in contrast to alloxan, is stable in aqueous media at physiological pH. Using rat islets of Langerhans, we have studied the acute effects of DHU on B cell function. Glucose-stimulated insulin release was markedly inhibited by DHU, the concentration of DHU giving 50% inhibition (I50) was 1 mmol/l; this was lowered to 0.5 mmol/1 when the islets were exposed to DHU for 5 min before elevation of glucose concentration. The basis for this change appeared to be a protective effect of glucose, since the inclusion of 3-0-methylglucose during pre-incubation with DHU also attenuated the subsequent inhibition of glucose-stimulated insulin release. The inhibitory effect on glucose-stimulated insulin release of a 5-min exposure to DHU persisted throughout a subsequent 120-min period in the absence of DHU. DHU also inhibited insulin release stimulated by mannose (20 mmol/l) or by 2-ketoisocaproate (20 mmol/l) with I50 of 1 and 0.5 mmol/l respectively. Concentrations of DHU up to 1 mmol/l had no significant effect on islet glucose oxidation or ATP content; 5 mmol/l DHU did not affect the rate of glucose oxidation, but lowered the ATP content by 30% without pre-incubation and by 60% in islets pre-incubated for 5 min with DHU before addition of glucose. Inhibitory effects of DHU were also found on rates of incorporation of [3H]-leucine into insulin plus proinsulin and into total islet protein; however, these parameters were less sensitive to DHU than was insulin release. These effects of DHU were similar to those of alloxan. These data suggest that DHU is an important new tool for studying the mechanism of action of B cell cytotoxic agents; in addition, the fact that DHU is a potential metabolite of uric acid could have relevance to the aetiology of diabetes mellitus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00253202
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  • 4
    Electronic Resource
    Electronic Resource
    Insulin secretory responses of a clonal cell line of simian virus 40-transformed B cells (1986)
    Springer
    Diabetologia 29 (1986), S. 727-733 
    Details
    ISSN: 1432-0428
    Keywords: Cell line ; insulin secretion ; HIT cells ; B cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have evaluated the potential of the clonal insulin-secretory cell line HIT-T15 as a model system for investigating stimulus-secretion coupling in pancreatic B cells. In contrast to other cell lines, HIT cell insulin secretion was consistently stimulated 2- to 3-fold by D-glucose. The maximally effective concentration of glucose was 10 mmol/1; between 2 and 10 mmol/l glucose the increase in insulin release was paralleled by an increased rate of glucose oxidation. The main characteristics of glucose-stimulated insulin release by HIT cells were essentially similar to those of normal islets. Thus, the response was (1) specific for metabolizable sugars (D-mannose and D-glyceraldehyde stimulated insulin release but L-glucose and D-galactose were ineffective); (2) markedly dependent on extracellular Ca2+ concentration; (3) potentiated by forskolin, glucagon, acetylcholine and 12-0-tetradecanoyl phorbol 13-acetate; (4) inhibited by adrenaline or somatostatin; (5) showed a biphasic pattern of release in perifusion experiments, with both phases being potentiated by forskolin. The secretory response of the HIT cells to amino acids was also similar to that of normal islets. Thus, L-leucine and its deamination product 2-ketoisocaproate were effective stimuli, whereas L-isoleucine and L-glutamine were ineffective. Insulin release from HIT cells could also be evoked by the sulphonylureas glibenclamide and tolbutamide and by an increase in concentration of extracellular K+ to 40 mmol/1. The content of cyclic AMP in HIT cells was increased modestly by glucose but not by an increase in extracellular K+. Forskolin elicited a 4-fold increase in cyclic AMP content. We conclude that HIT cells retain the essential features of the insulin secretory response of normal B cells and represent an important tool for further biochemical characterisation of the secretory system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00870283
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  • 5
    Electronic Resource
    Electronic Resource
    Protein phosphorylation and beta-cell function (1994)
    Springer
    Diabetologia 37 (1994), S. S21 
    Details
    ISSN: 1432-0428
    Keywords: Protein kinase ; phosphorylation ; protein phosphatase ; beta cell ; insulin secretion ; sulphonylurea receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The central role of reversible protein phosphorylation in regulation of beta-cell function is reviewed and the properties of the protein kinases so far defined in beta cells are summarised. The key effect of Ca2+ to initiate insulin secretion involves activation of a Ca2+/calmodulin-dependent protein kinase. Potentiation of secretion by agents activating protein kinase A or C appears to involve an increase in the sensitivity of the secretory system to intracellular Ca2+. The effects of MgATP on the binding of [3H]-glibenclamide to the beta-cell sulphonylurea receptor suggest that the properties of this receptor, which controls the activity of ATP-sensitive K-channels, are modulated by phosphorylation. The identity of the kinases and phosphatases responsible is not known but the presence in beta-cell membranes of various kinases not dependent on Ca2+ or cyclic AMP, and including tyrosine kinase, is documented, together with the presence of both Ca2+-dependent and Ca2+-independent protein phosphatases. Protein phosphorylation is also involved in regulation of beta-cell Ca2+ fluxes and evidence is presented that protein kinase C activation inhibits Ca2+ signalling by reducing influx of Ca2+ into the beta cell. The identity of the Ca2+/calmodulin-dependent protein kinase activity in beta cells is discussed. Comparison of its properties towards substrates and inhibitors with those of brain Ca2+/calmodulin-dependent protein kinase II suggests that the beta-cell enzyme may be similar or identical to the brain enzyme. Evidence from Northern and Western blotting experiments supports this conclusion. These findings are incorporated in a model for control of insulin secretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400822
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  • 6
    Electronic Resource
    Electronic Resource
    Glucose modulation of ATP-sensitive K-currents in wild-type, homozygous and heterozygous glucokinase knock-out mice (1998)
    Springer
    Diabetologia 41 (1998), S. 654-659 
    Details
    ISSN: 1432-0428
    Keywords: Keywords ATP-sensitive K-current ; glucokinase ; beta cell ; insulin secretion ; MODY.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary One type of maturity-onset diabetes of the young (MODY2) is caused by mutations in the glucokinase gene, a key glycolytic enzyme in the beta cell and liver. Glucose fails to stimulate insulin secretion in mice in which the glucokinase gene has been selectively knocked out in the beta cell. We tested the hypothesis that this effect results from defective metabolic regulation of beta cell ATP-sensitive potassium (KATP) channels. Glucose had little effect on KATP currents in homozygous (-/-) mice but inhibited KATP currents in wild-type (+/+) and heterozygous ( + /-) mice with EC50 of 3.2 mM and 5.5 mM, respectively, in newborn animals, and of 4.7 mM and 9.9 mM, respectively, in 1.5-year-old mice. Glucose (20 mmol/l) did not affect the resting membrane potential of -/- beta cells but depolarised wild-type and + /- beta cells and induced electrical activity. In contrast, 20 mmol/l ketoisocaproic acid or 0.5 mmol/l tolbutamide depolarised all three types of beta-cell. These results support the idea that defective glycolytic metabolism, produced by a loss (-/- mice) or reduction ( + /- mice) of glucokinase activity, leads to defective KATP channel regulation and thereby to the selective loss, or reduction, of glucose-induced insulin secretion. [Diabetologia (1998) 41: 654–659]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050964
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  • 7
    Electronic Resource
    Electronic Resource
    The hypoglycaemic and insulinotropic activity of Tinospora crispa: studies with human and rat islets and HIT-T15 B cells (1989)
    Springer
    Diabetologia 32 (1989), S. 354-359 
    Details
    ISSN: 1432-0428
    Keywords: Tinospora crispa ; insulin secretion ; hypoglycaemic ; insulinotropic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In Malaysia, Tinospora crispa extract is taken orally by Type 2 (non-insulin-dependent) diabetic patients to treat hyperglycaemia. We have evaluated the claimed hypoglycaemic property by adding aqueous extract to the drinking water of normal and alloxan-diabetic rats. After one week, fasting blood glucose levels were significantly (p〈0.01) lower and serum insulin levels were significantly (p〈0.01) higher in treated diabetic animals (10.4±1.0 mmol/l and 12.8±1.1 μU/ml respectively) compared to untreated diabetic controls (17.4±1.7 mmol/l and 8.0±0.7 μU/ml respectively). The insulinotropic action of T. crispa was further investigated in vitro using isolated human or rat islets of Langerhans and HIT-T15 cells. In static incubations with rat islets and HIT-T15 B cells, the extract induced a dosage dependent stimulation and potentiation of basal and glucose-stimulated insulin secretion respectively. This insulinotropic effect was also evident in perifused human and rat islets and HIT-T5 B-cells. The observations that (i) in all three models insulin secretory rates rapidly returned to basal levels on removal of the extract and (ii) in rat islets, a second challenge with T. crispa induced an additional, stimulated response, are all consistent with physiological release of insulin by B cells. Moreover, the rate of HIT-T15 glucose utilisation was not affected by incubation with T. crispa, suggesting that the cells were viable throughout. These are the first studies to provide biochemical evidence which substantiates the traditional claims for an oral hypoglycaemic effect of Tinospora crispa, and which also show that the hypoglycaemic effect is associated with increased insulin secretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00277258
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  • 8
    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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    Paper (German National Licenses)
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