The stimulus-secretion coupling of amino acid-induced insulin release. II. Sensitivity to K+, NH4+ and H+ of leucine-stimulated islets.

The insulinotropic action of L-leucine is thought to be tightly coupled with the metabolism of this amino acid in pancreatic islet cells. Consistent with such a view, the removal of extracellular K+ severely impaired L-leucine deamination and oxidation and L-leucine-stimulated insulin release. L-leucine increased the NH4+ content of islet cells. Exogenous NH4+ inhibited more markedly 45Ca net uptake and insulin release in islets exposed to L-leucine than in islets stimulated by D-glucose, D-glyceraldehyde or alpha-ketoisocaproate, all nutrients being used at concentrations of equal insulinotropic capacity. The islets exposed to L-leucine also differed from those stimulated with D-glucose by a somewhat higher 45Ca net uptake relative to insulin output, and an increased secretory activity in response to extracellular or intracellular acidification. It is proposed that in the islets exposed to L-leucine, an alteration in the islet content of NH4+ and possibly H+ interferes with the normal coupling between metabolic and secretory events.