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Research Article Free access | 10.1172/JCI109969

Evidence for the Involvement of Na/Ca Exchange in Glucose-induced Insulin Release from Rat Pancreatic Islets

Eberhard G. Siegel, Claes B. Wollheim, Albert E. Renold, and Geoffrey W. G. Sharp

Institut de Biochimie Clinique, University of Geneva, 1211 Geneva 4, Switzerland

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Institut de Biochimie Clinique, University of Geneva, 1211 Geneva 4, Switzerland

Find articles by Wollheim, C. in: PubMed | Google Scholar

Institut de Biochimie Clinique, University of Geneva, 1211 Geneva 4, Switzerland

Find articles by Renold, A. in: PubMed | Google Scholar

Institut de Biochimie Clinique, University of Geneva, 1211 Geneva 4, Switzerland

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Published November 1, 1980 - More info

Published in Volume 66, Issue 5 on November 1, 1980
J Clin Invest. 1980;66(5):996–1003. https://doi.org/10.1172/JCI109969.
© 1980 The American Society for Clinical Investigation
Published November 1, 1980 - Version history
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Abstract

Glucose-induced inhibition of Ca++ extrusion from the β-cell may contribute to the rise in cytosol Ca++ that leads to insulin release. To study whether interference with Na/Ca exchange is involved in this inhibition the effects of glucose were compared to those of ouabain. This substance inhibits Na/K ATPase, decreases the transmembrane Na+ gradient in islets, and thus interferes with Na/Ca exchange. Collagenase isolated rat islets were maintained for 2 d in tissue culture with a trace amount of 45Ca++. Insulin release and 45Ca++ efflux were then measured during perifusion. In Ca++-deprived medium (to avoid changes in tissue specific radioactivity) 16.7 mM glucose inhibited 45Ca++ efflux. Initially 1 mM ouabain inhibited 45Ca++ efflux in a similar fashion, the onset being even faster than that of glucose. The effects of 16.7 mM glucose and ouabain were not additive, indicating that both substances may interfere with Na/Ca exchange. In the presence of Ca++, 16.7 mM glucose induced biphasic insulin release. Ouabain alone caused a gradual increase of insulin release. Again, the effects of ouabain and 16.7 mM glucose were not additive. In contrast, at a submaximal glucose concentration (7 mM) ouabain enhanced both phases of release. An important role for Na/Ca exchange is suggested from experiments in which Ca++ was removed at the time of glucose-stimulation (16.7 mM). The resulting marked inhibition of insulin release was completely overcome during first phase by ouabain added at the time of Ca++ removal; second phase was restored to 60%. This could be due to the rapid inhibitory action of ouabain on Ca++ efflux thereby preventing loss of cellular calcium critical for glucose to induce insulin release. It appears, therefore, that interference with Na/Ca exchange is an important event in the stimulation of insulin release by glucose.

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