Studies of pancreatic alpha cell function in normal and diabetic subjects

immunoassay with a relatively high degree of speci-ficity for pancreatic glucagon made possible studies of alpha cell function in healthy nondiabetic subjects and in patients with diabetes mellitus. In the former group mean fasting plasma glucagon averaged 108,uAg/ml (SEAI ±+10). In 12 juvenile-type diabetics fasting gluca-gon averaged 110 (±9) and in 33 adult-type diabetics the average was 114 (±8). The diabetic averages did not differ significantly from the nondiabetic subjects; however, when hyperglycemia was induced by glucose infusion in the nondiabetic subjects so as to simulate the fasting hyperglycemia of the diabetics, mean gluca-gon fell to 57 /Ag (±8), which was significantly below the diabetic mean. In 28 healthy subjects the infusion of arginine elicited a rise in glucagon of at least 100 isg/ml with a peak level averaging 331 Ayg/ml (±22) at 40 min. This response to arginine was diminished but not abolished during hyperglycemia induced by simultaneous glucose infusion. In everyone of 45 diabetic subjects tested the infusion of arginine elicited a rise in glucagon of at least 140 pztg/ml to levels significantly greater than in nondiabetics. The peak glucagon level in juvenile-type diabetics averaged 458 ui*g/ml (SEM ±36) and in adult-type diabetics averaged 452 twg/ml (SEM +38). The glucagon response to arginine was unrelated to dura-tion of diabetes, to body weight, type of diabetic treat-ment, or to other known factors. Marked hyperrespon-siveness of glucagon to arginine infusion was observed in two patients with advanced Kimmelsteil-Wilson dis-ease. Glucagon levels were markedly elevated in certai