Stimulus-secretion coupling of glucose-induced insulin release. Effect of intracellular acidification upon calcium efflux from islet cells

Abstract

When pancreatic islets were exposed to a medium of normal pH (7.4) equilibrated with a gaz mixture containing 30% (instead of 5%) CO2, the intracellular pH of the islet cells, as judged by the apparent space of distribution of 14C-DMO, was decreased. The intracellular acidification was associated with a delayed decrease of [U-14C] glucose oxidation, but no major change in glucose-stimulated proinsulin biosynthesis, 45 calcium net uptake, or insulin release. The increase in PCO2 provoked an immediate and sustained decrease in the fractional outflow rate of 45Ca from prelabeled and perfused islets. The latter decrease was most marked under conditions associated with stimulated 40Ca-45Ca exchange (i.e., at glucose 16.7 mM and normal Ca2+ concentration), but was also present when a process of Na+-Ca2+ countertransport accounted for the major part of 45Ca efflux (e.g., in the absence of both glucose and extracellular Ca2+). These findings are compatible with the view that the generation of H+ derived from the metabolism of glucose in islet cells plays a role in the sugar-induced decrease in 45Ca fractional outflow rate.