Insulin Response to Glucagon: The Opposing Effects of Diabetes and Obesity

Abstract

Glucose and immunoreactive insulin responses to glucagon were studied in thirty-seven subjects with varying degrees of relative body weight and glucose tolerance. Glucagon was administered intravenously as an infusion (0.5 mg./30 min.), followed by the acute injection of 1.0 mg. Insulin and glucose levels rose concomitantly during the infusion, but only insulin values increased significantly following the acute injection, providing separation of the glycogenolytic and insulinogenic properties of glucagon. During the 30 min. following the glucagon injection, glucose levels fell to normal in the nondiabetic subjects but remained elevated among the diabetics. Obesity was associated with elevated basal insulin levels related to the degree of adiposity (r = .402, p < .02) but independent of glucose tolerance (r = < .030). In all subjects, the insidin responses to both glucagon infusion and injection were in turn related to the basal insulin values. The insulin response to glucagon, when expressed as per cent increment above basal in order to correct for the effect of varying degrees of insulin sensitivity as reflected in that basal level, was in all subjects related in a reciprocal manner to the degree of glucose intolerance as reflected by fasting glucose values (r = 0.891, p < .001). Thus, progressive glucose intolerance was associated with progressively impaired insulin secretion. Direct comparison of subjects classified on the basis of obesity or diabetes confirmed the exaggerating influence of obesity and the limiting effect of diabetes upon the insulin response to glucagon.