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 gamma-globulin to bind endogenously released somatostatin, and the insulin and glucagon secretion of these islets was compared with that of islets incubated in gamma-globulin isolated from nonimmune serum. Islets incubated in antisomatostatin gamma-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 Vmax was increased, but the apparent Km was unaltered; for glucose-suppression of glucagon release the threshold was increased, maximal suppression was decreased, but the apparent Ki was unaltered. The augmentative effect of the antisomatostatin gamma-globulin was most prominent at 4 mM glucose for insulin release and at 8mM glucose for glucagon release, but was not limited to glucose since both insulin and glucagon release stimulated by arginine were also augmented by antisomatostatin gamma-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.