Insulin/C-peptide response to intravenous glucagon

The C-peptide and insulin secretory responses to increasing doses of iv glucagon (1, 2, 5, 10 μg/kg body weight and I mg (only diabetics)) were investigated in six lean non-insulin-dependent diabetic patients and six normal subjects, matched for body weight and fasting blood glucose concentrations. A well defined relationship between glucagon dose and the C-peptide/insulin response was observed in both groups. The course of the dose-response curves was significantly different in diabetics. The maximal obtainable C-peptide response (E-max) was reduced to 53% of the response in normal subjects (P = 0.037), and the insulin response was reduced to 52% (P = 0.014). E-max was reached in diabetics with only 10 μg/kg of glucagon, whereas higher doses seem to be needed in the control group. However, the glucagon dose causing 50% of E-max (ed50) was not significantly higher. Thus, the widely accepted use of 1 mg of glucagon to test residual beta cell function secures a maximal response of both insulin and C-peptide in non-insulin-dependent diabetic subjects. In addition, our data support the theory that beta cell deficiency is a basic feature of non-insulin-dependent diabetes.