Modulation of Fatty Acid Metabolism by Glucagon in Man. II. Effects in Insulin-deficient Diabetics

The potential role of glucagon in the pathogenesis of diabetic ketogenesis was examined by intravenous glucagon administration (1.0 mug/kg. body weight) in five insulin-dificient diabetic subjects. The metabolic response was defined by examining the changes in the plasma concentration of insulin, glucose, free fatty acids (FFA), triglycerides, betahydroxybutyrate, and acetoacetate in comparison to those changes occuring in five nondiabetic control subjects tested under identical experimental conditions. Our results demonstrate that in the absence of endogenous insulin secretion, exogenous glucagon administration results in an enhanced ketonemia indipendent of the rise of FFA substrate. This augmented ketogenic response to glucagon in diabetic subjects was not reflected in the dynamics of glucose regulation, with similar changes in blood glucose concentration occurring in both diabetic and nondiabetic populations. These data demonstrate that glucagon may potentiate ketonemia in insulin-deficient diabetics, although the mechanism mediating this augmentation is not defined. Since the rise in FFA substrate was indistinguishable in the diabetic as compared to the control group, increased hepatic conversion of FFA substrate into ketone bodies is suggested.