Dose-kinetics of pancreatic glucagon responses to arginine and glucose in subjects with normal and impaired pancreatic B cell function

Summary Pancreatic glucagon responses to different amounts of intravenous arginine and glucose were studied in 10 insulin-dependent diabetics, 14 healthy controls (high insulin responders) and 15 subjects with decreased insulin response to glucose but normal intravenous glucose tolerance (low insulin responders). The dose-kinetics of the glucagon response was studied by using four different arginine doses. The suppressive effect of glucose was evaluated by infusing three glucose doses during a submaximal stimulation with arginine. The diabetics were tested first when under fair metabolic control and then following intensive treatment with insulin to produce near-normalisation of blood glucose. Finally, five subjects underwent insulin-induced hypoglycaemia. The changes in plasma glucagon and blood -amino-nitrogen in response to the four arginine doses were significantly correlated in all groups but the slope of the dose response curve was steeper in the poorly controlled-diabetics than in the non-diabetics. These diabetics displayed higher fasting plasma glucagon values than healthy controls (high insulin responders) (224±4 versus 151±22 pg/ml, p<0.01), higher plasma glucagon responses to arginine and an absence of inhibition by glucose of the arginine-stimulated glucagon release. In strictly controlled diabetic patients, fasting plasma glucagon levels (176±16 pg/ml) were not significantly different from healthy controls, the glucagon response to arginine returned to the normal range, A cell suppressibility by glucose was restored and A cell stimulation by hypoglycaemia reappeared. In the low insulin responders, fasting plasma glucagon was not different from that of high responders (107±12 pg/ml), the slope of the dose response curve to arginine was similar in both groups and the A cells were inhibited by glucose to a similar extent. These results support the concept that islet A cell dysfunction in diabetes is not a primary phenomenon.