It is now clear that the predominant metabolic effect of sulfonylurea compounds is to release insulin from pancreatic beta cells. In addition, assays by Yalow, Black, Villazon and Berson (1) of insulin concentrations in peripheral blood indicate that the secretory potency of sulfonylureas is substantially weaker than that of glucose. More quantitative comparison of insulin-releasing activities of individual substances, however, requires knowledge of both the concentration of insulin 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 pancreatic 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-inducing agent was injected into a peripheral vein. Although glucose and three sulfonylurea compounds 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 secretion.
METHODSMongrel dogs of either sex, weighing between 10 and 15 kg, were used in all experiments. During a quarantine period of 14 days, animals were metabolically stabilized 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, intact dogs were used after a 24-hour fasting period.