Prior Exposure to High Glucose Augments Depolarization-Induced Insulin Release by Mitigating the Decline of ATP Level in Rat Islets

A brief exposure to elevated glucose augments the insulin secretory response of islets to subsequent stimulation. The site of this priming effect of glucose in the mechanism of the regulation of insulin secretion is not completely known, however. Insulin release triggered by a depolarizing concentration of K+ in the presence of basal glucose is markedly enhanced in primed rat islets. To clarify the role of priming on Ca2+ and ATP efficacy in the exocytotic apparatus, islets were electrically permeabilized to vary the intracellular Ca2+ and ATP concentrations according to the extracellular medium, and insulin release was evaluated. Ca2+ and ATP efficacy in Ca2+- and ATP-dependent insulin secretion was not affected by priming, and alteration of the intracellular Ca2+ concentration after depolarization cannot account for the phenomenon. There was no difference in ATP content before depolarization between nonprimed and primed islets. Moreover, the decline in ATP level after depolarization with basal glucose w...