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

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, ⁴⁵calcium net uptake, or insulin release. The increase in p_CO2 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.