The contribution of endogenous insulin secretion to the ketogenic response to glucagon in man.

The magnitude and direction of the lipolytic and ketogenic responses following exogenous glucagon administration is controversial and consideration of the possible role of endogenous insulin secretion upon these events has not been clarified. The present study examines the role of endogenous insulin secretion in modulating the net lipolytic and ketogenic activity of glucagon. Three groups characterized by different levels of endogenous insulin secretory capacity were studied. In all three groups, the responses in plasma insulin, betahydroxybutyrate, and free fatty acids were observed following bolus administration of 1.0 mug/kg glucagon. In the obese subjects with increased endogenous insulin secretion, glucagon administration resulted in a decline below basal levels of both free fatty acid and betahydroxybutyrate. In the diabetic subjects with no demonstrable endogenous insulin secretion, glucagon administration was followed by a rise in plasma free fatty acids and an exaggerated rise in plasma betahydroxybutyrate. The normal control group exhibited a response in betahydroxybutyrate midway between the obese and diabetic groups. These obwervations support the thesis that the magnitude of endogenous insulin secretion modulates the lipolytic and ketogenic actions of glucagon in man.