Quantitative effects of glucose, sulfonylureas, salicylate, and indole-3-acetic acid on the secretion of insulin activity into pancreatic venous

It is now clear that the predominant metabolic effect of sulfonylurea compounds is to release in-sulin from pancreatic beta cells. In addition, as-says by Yalow, Black, Villazon and Berson (1) of insulin concentrations in peripheral blood indi-cate that the secretory potency of sulfonylureas is substantially weaker than that of glucose. More quantitative comparison of insulin-releasing ac-tivities of individual substances, however, re-quires knowledge of both the concentration of in-sulin in pancreatic venous blood, and the latter's rate of flow. A suitable closed circuit enabling these measurements was devised by Metz (2), who determined total insulin outflow from the pancreaticoduodenal vein draining the right pan-creatic limb in dogs during glucose infusion into the femoral vein. The latter technic was employed in the present study to determine total secretion of insulin activity from a segment of dog pancreas for 30 minutes after glucose or a hypoglycemia-induc-ing agent was injected into a peripheral vein. Although glucose and three sulfonylurea com-pounds all promptly initiated release of insulin, glucose was by far the most potent insulogenic substance. In contrast, neither salicylate nor indole-3-acetic acid altered the rate of insulin se-cretion. METHODS Mongrel dogs of either sex, weighing between 10 and 15 kg, were used in all experiments. During a quaran-tine period of 14 days, animals were metabolically stabi-lized on a daily ration of meat and Purina laboratory chow, which provided approximately 60 g protein, 20 g fat and 90 g carbohydrate. In early experiments, intac