Characteristics of the inhibitory effect of alkalosis on insulin secretion

Glucose-induced insulin secretion by the perfused sodium pentobarbital-anesthetized-rat pancreases was studied under different extracellular pH ranging from 7.4 to 7.8. Under our experimental conditions the amount of insulin released was inversely correlated to the pH increase. Besides, metabolic (CO2H- excess) or gaseous (low pCO2) type of alkalosis, were equally effective inhibiting insulin secretion. During a 16.6 mM glucose stimulus, sequential modifications of extracellular pH (7.4-7.8-7.4) caused a dramatic decrease in insulin secretion during alkalosis and an enhancement of its release during the second 7.4 period. The installment and remotion of the inhibition followed almost immediately the changes in the pH of the perfusates. These findings indicate that extracellular diminution of H+ concentration produces a gradual and quickly reversible decrease upon glucose-induced insulin secretion. These characteristics suggest that the inhibitory effect may be mediated through changes in intracellular and/or transmembrane ion fluxes coupled to the variations in H+ concentration.