Stimulus-secretion coupling of arginine-induced insulin release. Functional response of islets to l-arginine and l-ornithine

Abstract

L-Arginine and L-ornithine stimulate insulin release from pancreatic islets exposed to d-glucose. This coincides with an increased outflow of 86Rb and 45Ca from prelabelled islets and an increased net uptake of 45Ca by the islets. In the presence of d-glucose, l-lysine stimulates insulin secretion to the same extent as l-arginine or l-ornithine, but the hormonal release is not further enhanced by combinations of these cationic amino acids. L-Arginine or L-ornithine failed to enhance insulin release evoked by either l-leucine or 2-ketoisocaproate. The inhibitor of ornithine decarboxylase d,l-α-difluoromethyl ornithine failed to affect the metabolism and insulinotropic action of d-glucose in pancreatic islets, and only caused a partial inhibition of the secretory response to either l-arginine or l-ornthine. The latter amino acids inhibited modestly but significantly d-glucose utilization and oxidation by pancreatic islets. These and complementary findings suggest that the secretory response to l-arginine and l-ornithine is not attributable to any major change in the overall oxidative catabolism of nutrients, but involves mainly a biophysical component, such as the depolarization of the plasma membrane by these cationic amino acids.