EFFECT OF INTERMITTENT ENDOGENOUS HYPERGLUCAGONEMIA ON GLUCOSE-HOMEOSTASIS IN NORMAL AND DIABETIC MAN

Infusions of glucagon causes only a transient increase in glucose production in normal and diabetic man. To assess the effect of intermittent endogenous hyperglucagonemia that might more closely reflect physiologic conditions, arginine (10 g over 30 min) was infused four times to 8 normal subjects and 13 insulin-dependent diabetic subjects (4 of whom were infused concomitantly with somatostatin to examine effects of arginine during prevention of hyperglucagonemia). Each arginine infusion was separated by 60 min. Diabetic subjects were infused throughout the experiments with insulin at rates (0.07-0.48 mU/kg per min) that had normalized base-line plasma glucose and rates of glucose appearance (Ra) and disappearance (Rd). Basal plasma glucagon and arginine-induced hyperglucagonemia were similar in both groups; basal serum insulin in the diabetics (16±1 μU/ml, P<0.05) exceeded those of the normal subjects (10±1 μU/ml, P<0.05) but did not increase with arginine. Serum insulin in normal subjects increased 15-20 μU/ml with each arginine infusion. In both groups each arginine infusion increased plasma glucose and Ra. Increments of Ra in the diabetics exceeded those of normal subjects, (P<0.02); Rd was similar in both groups. In normal subjects, plasma glucose returned to basal levels after each arginine infusion, whereas in the diabetics hyperglycemia persisted reaching 151±15 mg/dl after the last arginine infusion. When glucagon responses were prevented by somatostatin, arginine infusions did not alter plasma glucose or Ra. Conclusions: Infusion of arginine acutely increases plasma glucose and glucose production in man solely by stimulating glucagon secretion; physiologic increments in plasma glucagon (100-150 pg/ml) can result in sustained hyperglycemia when pancreatic beta cell function is limited.