The Stimulus-Secretion Coupling of Glucose-Induced Insulin Release - II. Interaction of Alkali and Alkaline Earth Cations[*]

Abstract

Glucose-induced insulin secretion is enhanced at high K⁺ concentrations (10 to 34 mEq/l), and in the presence of ouabain. It is reduced when Na⁺ is partially replaced by either Li⁺, Tris, or larger amounts of K⁺(87 to 115 mEq/l). The elevated rate of secretion observed at high K⁺ concentration (24 mEq/l) is markedly reduced by replacement of NaCl by sucrose. These data suggest that Na⁺ entry in the beta-cell favors insulin release. However, the stimulant action of glucose is increased when Na⁺ is replaced by choline and persists in a Na⁺-free medium, indicating that the influx of Na⁺ per se is not necessary for secretion to occur. It is suggested that alkali cations could influence insulin secretion through an altered handling of alkaline earth cations by the beta-cell. In favor of this hypothesis, it is shown that the beta-cell becomes unresponsive to Ba++ when Na+ is replaced by Li+, Tris, or large amounts of K+; whereas the elevated rates of secretion observed when Na⁺ is replaced by choline or moderate amounts of K⁺ are markedly reduced by the omission of Ca⁺⁺ from the incubation medium. The inhibitory effect of extracellular acidosis upon glucose-induced secretion could also be due, in part at least, to a reduced entry of Ca⁺⁺ in the beta-cell. These data support the concept that entry of Ca⁺⁺ might trigger the release of insulin and that the influence of alkali cations upon insulin release could be mediated by an alteration of this process.

Key words

Insulin Secretion - Sodium - Potassium - Lithium - Tris - Choline - Ouabain - Calcium - pH - Baryum

1 This work was supported in part by a grant from the Fonds National de la Recherche Scientifique (Brussels, Belgium) and a grant-in-aid from the Lilly Research Laboratories (Indianapolis, Indiana).

1 This work was supported in part by a grant from the Fonds National de la Recherche Scientifique (Brussels, Belgium) and a grant-in-aid from the Lilly Research Laboratories (Indianapolis, Indiana).