Antisomatostatin Gamma Globulin Augments Secretion of Both Insulin and Glucagon In Vitro: Evidence for a Physiologic Role for Endogenous Somatostatin in the Regulation of Pancreatic A- and B-Cell Function

To assess the effects of endogenous somatostatin on pancreatic islet A- and B-cell function, isolated rat islets were incubated in antisomatostatin γ-globulin to bind endogenously released somatostatin, and the insulin and glucagon secretion of these islets was compared with that of islets incubated in γ-globulin isolated from nonimmune serum. Islets incubated in antisomatostatin γ-globulin released significantly more insulin at 4, 8,16, and 32 mM glucose and significantly more glucagon at 8,16, and 32 mM glucose, P < 0.05–0.005. For glucose-stimulated insulin release the threshold was decreased, the V_max was increased, but the apparent K_m was unaltered; for glucose-suppression of glucagon release the threshold was increased, maximal suppression was decreased, but the apparent K_i was unaltered. The augmentative effect of the antisomatostatin γ-globulin was most prominent at 4 mM glucose for insulin release and at 8 mM glucose for glucagon release, but was not limited to glucose since both insulin and glucagon release stimulated by arginine were also augmented by antisomatostatin γ-globulin. These results provide evidence that endogenous somatostatin may act as a physiologic local regulator of both insulin and glucagon secretion and that its effect on insulin and glucagon secretion is dependent on the prevailing glucose concentration.