Role of Glucagon in the Glucoregulatory Response to Insulin-Induced Hypoglycemia in the Rat

Abstract

To characterize further the role of glucagon in the glucoregulatory response to hypoglycemia, the changes in the hepatic glucose production (Ra) and tissue uptake (Rd) after the injection of insulin (100 mU, i.v.) were measured in control and somatostatin-treated rats by using the primed constant infusion of glucose-2-³H. The physiologic glucagon hypersecretion due to hypoglycemia observed in controls was completely abolished by somatostatin. Hypoglycemia was slightly more pronounced in SRIF-treated rats than in controls; however, a clear tendency to recovery was recorded in both groups. Although the morphology of Ra response-curves was similar, the values of Ra were significantly lower in SRIF-treated rats throughout the experimental period. Glucose uptake showed in rats receiving somatostatin an initial increase of the same magnitude as in controls, but later it decreased more consistently. If the tissue sensitivity to insulin effect was expressed as metabolic clearance rate, no appreciable difference was recorded. These studies provide direct evidence that glucagon is involved in the metabolic reaction to insulin-induced hypoglycemia. However, the tendency to recovery from hypoglycemia shown by glucagon-deficient rats suggests that factors other than glucagon must play a more prominent role in the maintenance of glucose homeostasis in emergency situations such as represented by hypoglycemia induced by a large dose of exogenous insulin. 1 Presented in part at the 12th Annual Meeting of the European Association for the Study of Diabetes. Helsinki, September 3, 1976