Failure of Sulfonylureas to Suppress Plasma Glucagon in Man

Others² have reported that sulfonylureas suppress the release of glucagon and concluded that this is an important mechanism by which these compounds lower blood glucose. The studies reported here demonstrate the following: 1) oral administration of chlorpropamide for three days or rapid intravenous injection of tolbutamide did not induce a significant change in basal levels of immunoreactive glucagon (IRG) ; 2) intravenous infusion of tolbutamide in saline over thirty minutes did not evoke significant decreases in IRC; 3) tolbutamide added to solutions of arginine or of a mixture of ten amino acids (10-AA) failed to reduce the increases in IRG evoked by the infusion of these amino acid solutions in the absence of tolbutamide; and 4) tolbutamide injected rapidly at the midpoint of infusions of arginine or of 10-AA did not alter the steady rise in IRG induced by these amino acid solutions. In addition, tolbutamide failed to prevent hypoglycemia-induced increases in IRG. These results indicated that in man sulfonylureas do not suppress plasma levels of glucagon and that sulfonylurea-induced decreases in blood glucose are not mediated through suppression of glucagon release.