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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 13 (1977), S. 297-303 
    ISSN: 1432-0428
    Keywords: Isolated ; perfused pancreas ; glucagon release ; calcium ; glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using the isolated, perfused canine pancreas the importance of calcium for the normal secretory function of the pancreatic alpha cell was investigated. It was found that 1. increases in perfusate Ca++ from 1.3 to 4.8 mM and from 1.3 to 8.2 mM during perfusion with glucose concentrations of 25 and 150 mg/100 ml stimulate the release of both glucagon and insulin in a dose-related and a glucose-dependent fashion. The hormone responses to increases in calcium were, with few exceptions, biphasic 2. a ‘Ca++ free’ medium inhibited release of both hormones, and increases in perfusate glucose from 25 to 150 mg/100 ml were unable to suppress glucagon or to stimulate insulin. Addition of calcium (8.2 mM) resulted in re-establishment of the normal regulatory role of glucose upon release of both hormones, now being in a hyperactivated state by the high Ca++ concentration; 3. sudden Ca++ depletion of the perfusate from 2 mM at a glucose concentration of 200 mg/100 ml inhibited immediately the release of both hormones to very low levels, which remained low until the addition of Ca++ (2 mM). Ca++ is therefore an essential requirement for the normal secretory process of pancreatic glucagon, possibly involving uptake and accumulation within the A cell, as established for the B cell. It is suggested that Ca++ exerts its effect on the microtubular microfilamentous system.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Endothelin-1 ; islet of Langerhans ; mouse ; ion fluxes ; glucose ; insulin secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Endothelin-1 (ET-1), a potent endothelium-derived vasoconstrictor peptide, is secreted in response to insulin. Elevated circulating ET-1 levels have been found in patients with diabetes mellitus and vascular dysfunction. The question arises whether ET-1 acts as a direct modulator of insulin secretion. To test this, we studied the effects of ET-1 on isolated mouse islets of Langerhans. ET-1 (1 nmol/l-1 Μmol/l) dose-dependently stimulated insulin secretion from islets incubated in the presence of 16.7 mmol/l glucose (p〈0.05). The effect of ET-1 is glucose-dependent since no potentiation was found at 3.3 mmol/l glucose. Furthermore, ET-1 induced a large, transient increase in glucose-stimulated insulin secretion during islet perifusion in the presence (p〈0.001), but not in the absence, of extracellular Ca2+. The rate of 45Ca2+-efflux from 45Ca2+-prelabelled islets was transiently stimulated by ET-1 during perifusion at 16.7 mmol/l glucose in the presence of extracellular Ca2+ (p〈0.001). A short-lived increase in 45Ca2+-efflux was also observed in the absence of extracellular Ca2+ (p〈0.05). It is suggested that the effects of ET-1 on insulin secretion are critically dependent on influx via Ca2+-channels. In addition, ET-1 transiently enhanced 86Rb+-efflux from 86Rb+-prelabelled islets both in the presence (p〈0.001) and in the absence (p〈0.001) of extracellular Ca2+ suggesting that ET-1 does not elicit insulin secretion by inhibition of the potassium permeability. Our study provides evidence that ET-1 stimulates insulin secretion via a direct effect on the islets of Langerhans.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Diabetes ; streptozotocin ; somatostatin release ; glucagon release ; isolated canine perfused pancreas ; glucoreceptor ; glucose ; arginine ; isoproterenol ; calcium ; radioimmunoassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Somatostatin release from the isolated pancreas of 3 normal and 6 streptozotocin diabetic dogs has been measured in response to various stimuli to determine whether abnormalities in somatostatin release are present in the diabetic pancreas. Simultaneous measurement of glucagon secretion was also made. In the pancreas from normal dogs increases in perfusate glucose from 25 to 200 mg/100 ml induced a 2–3 fold increase in somatostatin release and a two thirds decrease in glucagon secretion. In contrast, in the diabetic pancreas glucose caused no change in the secretion of the two hormones. In the diabetic pancreas addition of insulin to the perfusate (25,000 μU/ml) for periods from 10 to 75 minutes aimed at restoring normal extracellular insulin levels in the islets failed to restore either somatostatin or glucagon secretion to normal. In contradistinction to the lack of effect of glucose, the somatostatin and glucagon responses to arginine (5 mmol/l), isoproterenol (2 ng/ml) and calcium (5 mmol/l) were normal in the diabetic pancreas. The data suggests the presence of a selective glucoreceptor abnormality of the D as well as of B and A cells in the streptozotocin diabetic dog.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Pancreas ; diabetes ; somatostatin ; glucagon ; insulin ; D-glyceraldehyde ; dihydroxyacetone ; mannoheptulose ; glucose ; arginine ; isolated perfused pancreas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pancreatic D and A cell function is deranged in streptozotocin diabetes. To investigate this, the effect of D-glyceraldehyde, dihydroxyacetone, D-mannoheptulose and glucose variations during arginine stimulation on the release of somatostatin and glucagon from the isolated pancreas of normal and streptozotocin diabetic dogs was studied. Concentrations of the trioses, D-glyceraldehyde (1.25 and 2.5 mmol/l) and dihydroxyacetone (11 mmol/l), which normally stimulate D cells, did not influence the release of somatostatin in the diabetic dog. However, the higher concentration of D-glyceraldehyde (5 mmol/l) suppressed D cell secretion in the diabetic animals at 0 and 8.3 mmol/l glucose. A cell secretion was significantly suppressed at the higher glucose level in response to both 2.5 and 5 mmol/l of the triose. This inhibition may be explained by a non-specific effect induced by the high dose of this triose. The addition of 5 mmol/l mannoheptulose, which normally reduces glucose-induced somatostatin secretion and stimulates glucagon release, did not affect hormone secretion. In both the diabetic and the normal animals, arginine (5 mmol/l) stimulated somatostatin and glucagon secretion. Although arginine was able to stimulate D and A cell secretion in the diabetic dogs, it was however unable to restore the response to changes in glucose concentration between 1.4 and 8.3 mmol/l to normal. These results demonstrate that the abnormal pancreatic D and A cell function in streptozotocin diabetes is characterised by an impaired response to glucose and certain glucose metabolites and probably results from a specific defect in glucose recognition.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Keywords Endothelin-1 ; islet of Langerhans ; mouse ; ion fluxes ; glucose ; insulin secretion.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Endothelin-1 (ET-1), a potent endothelium-derived vasoconstrictor peptide, is secreted in response to insulin. Elevated circulating ET-1 levels have been found in patients with diabetes mellitus and vascular dysfunction. The question arises whether ET-1 acts as a direct modulator of insulin secretion. To test this, we studied the effects of ET-1 on isolated mouse islets of Langerhans. ET-1 (1 nmol/l–1 μmol/l) dose-dependently stimulated insulin secretion from islets incubated in the presence of 16.7 mmol/l glucose (p 〈 0.05). The effect of ET-1 is glucose-dependent since no potentiation was found at 3.3 mmol/l glucose. Furthermore, ET-1 induced a large, transient increase in glucose-stimulated insulin secretion during islet perifusion in the presence (p 〈 0.001), but not in the absence, of extracellular Ca2 + . The rate of 45Ca2 + -efflux from 45Ca2 + -prelabelled islets was transiently stimulated by ET-1 during perifusion at 16.7 mmol/l glucose in the presence of extracellular Ca2 + (p 〈 0.001). A short-lived increase in 45Ca2 + -efflux was also observed in the absence of extracellular Ca2 + (p 〈 0.05). It is suggested that the effects of ET-1 on insulin secretion are critically dependent on influx via Ca2 + -channels. In addition, ET-1 transiently enhanced 86Rb + -efflux from 86Rb + -prelabelled islets both in the presence (p 〈 0.001) and in the absence (p 〈 0.001) of extracellular Ca2 + suggesting that ET-1 does not elicit insulin secretion by inhibition of the potassium permeability. Our study provides evidence that ET-1 stimulates insulin secretion via a direct effect on the islets of Langerhans. [Diabetologia (1996) 39: 1030–1035]
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 16 (1979), S. 261-266 
    ISSN: 1432-0428
    Keywords: Perfused pancreas ; somatostatin ; insulin ; glucagon ; calcium ; acetylcholine ; glucose ; isoproterenol ; arginine ; radioimmunoassay ; dog pancreas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of calcium on somatostatin secretion was investigated in the isolated, perfused canine pancreas preparation and compared with those of acetylcholine, glucose, isoproterenol and arginine. Calcium (5 mmol/l) stimulated somatostatin release in a typical biphasic response pattern being about 5 times as potent as acetylcholine (1 μmol/l), arginine (5 mmol/l), and isoproterenol (2 ng/ml) while the release of insulin and glucagon in response to calcium and the other secretagogues were of the same magnitude. Somatostatin release increased progressively when perfusate calcium was increased step-wise from 0 through 1.25 and 2.5 to 5.0 mmol/l. Calcium stimulated the secretion of somatostatin in the absence of glucose. The stimulatory effect of calcium was, however, modulated by the glucose concentration being about twice as large at 200 mg/100 ml as at 25 mg/100 ml glucose in the perfusion medium.
    Type of Medium: Electronic Resource
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