Activation of Na channels in islet cells: metabolic and secretory effects.

Publisher Website
Google Scholar
Abstract
The role of changes in the permeability of the [rat] .beta.-cell plasma membrane to Na and Ca in the control of stimulus-secretion coupling was studied using veratridine in combination with varying levels of glucose. In the presence of 5.6 mM glucose, 200 .mu.M veratridine induced depolarization accompanied by a transient increase in the incidence of spike activity; these responses were prevented by 3.0 .mu.M tetrodotoxin (TTX). Veratridine (10 or 200 .mu.M) had divergent effects on insulin secretion and glycolytic flux when examined in the presence of varying levels of glucose (2.8-27.8 mM). Only 200 .mu.M veratridine enhanced insulin secretion with glucose .ltoreq. 8.4 mM. In comparison, 10 and 200 .mu.M veratridine potentiated glycolytic flux at levels of glucose .gtoreq. 8.4 and .gtoreq. 5.6 mM, respectively. TTX blocked the secretory and metabolic responses due to veratridine, but not that due to glucose. A Ca-free medium or the addition of Co completely inhibited the secretory, but not the metabolic response to veratridine. The addition of 1.0 mM ouabain blocked the metabolic response to veratridine, but did not influence the secretory response. A selective increase in the cationic permeability of the .beta.-cell membrane is apparently a sufficient event to trigger insulin release. The increase in glucose metabolism may serve to supply energy for the maintenance of the electrochemical gradient.