Evaluation of Alpha-Cell Function by Infusion of Alanine in Normal, Diabetic and Obese Subjects

To evaluate alpha-cell function, L-alanine was infused intravenously (0.15 g per kilogram of body weight) to healthy controls, nonobese and obese diabetic patients and obese subjects with normal glucose tolerance. Alanine induced a consistent rise in plasma glucagon in normal subjects that was increased by starvation. An augmented glucagon response was also observed in nonobese diabetic patients. In contrast, the glucagon response was diminished in obese subjects, even in the presence of diabetes. No glucagon increment occurred in two diabetic patients with pancreatic insufficiency. For all subjects, the rise in plasma glucagon induced by alanine was directly proportional to the rise in plasma glucose. Thus, the alpha-cell response to alanine appears to be augmented in diabetes and starvation and suppressed by obesity, even when accompanied by diabetes. In each of these circumstances, the glucagon response is reflected in the rise in blood glucose. Infusion of alanine may provide a useful means of evaluating alpha-cell function in a variety of metabolic states.