Endothelin-1 and endothelin-3 stimulate insulin release by isolated rat pancreatic islets

The mechanism of synergism between glucose and adenosine 3',5'-cyclic monophosphate (cAMP) on insulin release has been studied. Synergism may result from 1) inhibition of Na+-Ca2+ exchange by glucose and 2) a cAMP-induced sensitization of the release machinery to Ca2+. To distinguish between these two possibilities, isolated rat pancreatic islets were perifused with agents that raise intracellular levels of cAMP [3-isobutyl-1-methylxanthine (IBMX) and forskolin] and others that increase intracellular concentrations of Ca2+ either by blocking Na2+-Ca2+ exchange (ouabain and choline-Ringer solution) or by causing increased Ca2+ influx (KCl, carbachol, and 10 mM Ca2+). The results indicate that both the combination of cAMP and increased Ca2+ influx or blocked Na2-Ca2+ exchange and increased Ca2+ influx potentiated insulin release. When the relative potentiating abilities of cAMP and blocked Na2+-Ca2+ exchange were compared by determining the individual effects of IBMX and 1 mM ouabain (a concentration that causes similar inhibition of 45C2+ efflux as 16.7 mM glucose) in the presence of carbachol, cAMP was only 1.4 times more potent as a potentiating agent than blocked Na+-Ca2+ exchange. The greatest potentiation of insulin release was observed when Na+-Ca2+ exchange was blocked in the presence of increased levels of intracellular cAMP.

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Insulin release from isolated rat pancreatic islets induced by α-ketoisocaproic acid, L-leucine, D-glucose or D-glyceraldehyde: Effect of gastric inhibitory polypeptide or glucagon

Molecular and Cellular Endocrinology ◽

10.1016/0303-7207(77)90061-2 ◽

1977 ◽

Vol 7 (2) ◽

pp. 115-123 ◽

Cited By ~ 10

Author(s):

P. Schauder ◽

B. Schindler ◽

U. Panten ◽

J.C. Brown ◽

H. Frerichs ◽

...

Keyword(s):

Pancreatic Islets ◽

Insulin Release ◽

Gastric Inhibitory Polypeptide ◽

Rat Pancreatic Islets ◽

Isolated Rat

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Calcitonin Inhibition of Insulin Release from Isolated Rat Pancreatic Islets

Diabetes ◽

10.2337/diab.35.1.58 ◽

1986 ◽

Vol 35 (1) ◽

pp. 58-60 ◽

Cited By ~ 7

Author(s):

A. Alwmark ◽

M. W. Stavinoha ◽

C. W. Cooper ◽

G. H. Greeley ◽

J. C. Thompson

Keyword(s):

Pancreatic Islets ◽

Insulin Release ◽

Rat Pancreatic Islets ◽

Isolated Rat

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Effects of tetracaine on insulin release and calcium handling by rat pancreatic islets

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1987.252.6.e727 ◽

1987 ◽

Vol 252 (6) ◽

pp. E727-E733

Author(s):

S. M. el Motal ◽

M. C. Pian-Smith ◽

G. W. Sharp

Keyword(s):

Tissue Culture ◽

Pancreatic Islets ◽

Insulin Release ◽

Culture Conditions ◽

Isolated Islets ◽

Calcium Handling ◽

Ca Channels ◽

Rat Pancreatic Islets ◽

Voltage Dependent ◽

Stimulate Insulin Release

The effects of tetracaine on insulin release and 45Ca2+ handling by rat pancreatic islets have been studied under basal (2.8 mM glucose), glucose-stimulated (5.6, 8.3, and 16.7 mM glucose), and 3-isobutyl-1-methylxanthine (IBMX)-stimulated conditions. Islets were isolated by the use of collagenase and used either directly (freshly isolated islets) or after a period under tissue culture conditions. Tetracaine was found to stimulate insulin release under basal conditions, to inhibit glucose-stimulated insulin release, and to potentiate insulin release stimulated by IBMX. In studies on the mechanisms underlying these effects, tetracaine was found to decrease glucose-stimulated net retention of 45Ca2+ (by an action to block the voltage-dependent Ca channels) and to mobilize Ca2+ from intracellular stores. These two actions form the basis for the inhibition of glucose-stimulated insulin release, which depends heavily on Ca2+ entry via the voltage-dependent channels and the synergism with IBMX to potentiate release. No inhibition of IBMX-stimulated release occurs because IBMX does not use the voltage-dependent channels to raise intracellular Ca2+.

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