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Calcium-induced insulin release in monolayer culture of the endocrine pancreas. Studies with ionophore A23187

Blondel, B
Trueheart, P A
Renold, A E
Sharp, G W
Published in Journal of Biological Chemistry. 1975, vol. 250, no. 4, p. 1354-60
Abstract The role of Ca2+ on insulin release has been studied by the use of ionophore A23187. The ionophore complexes divalent cations and permits Ca2+ entry into cells by acting as a carrier in the plasma membranes. Cultured cells obtained by enzymatic digestion of pancreases from newborn rats were studied on the 3rd day of culture. With Ca2+ in the incubation medium the ionophore induced sustained insulin release even in the absence of glucose. Optimal effects of the ionophore were observed at 3 and 10 mug per ml in the presence of 0.3 to 1.0 mM Ca-2+. Under these conditions the insulin release was greater than that caused by 16.7 mM glucose. A graded response was observed to changes in Ca-2+ concentration from 0.1 to 1.0 mM Ca-2+. Higher Ca-2+ concentrations caused a large amount of insulin to be released promptly, but the release was not sustained. Mg-2+ and Sr-2+ were not found to substitute for Ca-2+. Ba-2+ at 0.3 mM stimulated insulin release even in the absence of ionophore. Cyclic adenosine 3':5'-monophosphate was able to increase ionophore-induced insulin release. The alpha-adrenergic effect of epinephrine to inhibit insulin release was not observed in the presence of Ca-2+ and the ionophore, and a stimulatory effect of epinephrine was seen. This unusual stimulatory effect of epinephrine was blocked by propranolol indicating a beta-adrenergic mechanism for epinephrine. It is concluded that Ca-2+, which plays an essential role in the stimulus-secretion coupling, can alone initiate and cause sustained insulin release.
Keywords AnimalsAnti-Bacterial Agents/pharmacologyAntibodiesBarium/pharmacologyCalcium/pharmacologyCarboxylic Acids/pharmacologyCells, CulturedCyclic AMP/pharmacologyEpinephrine/pharmacologyGlucose/pharmacologyInsulin/metabolismIslets of Langerhans/drug effects/metabolismMagnesium/pharmacologyPropranolol/pharmacologyRatsStrontium/pharmacology
PMID: 163251
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WOLLHEIM, Claes et al. Calcium-induced insulin release in monolayer culture of the endocrine pancreas. Studies with ionophore A23187. In: Journal of Biological Chemistry, 1975, vol. 250, n° 4, p. 1354-60. https://archive-ouverte.unige.ch/unige:40545

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Deposited on : 2014-09-26

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