Insulin and C‐peptide Secretory Responses to Glucagon in Man: Studies on the Dose‐Response Relationships

. The present study investigated the insulin and C-peptide secretory responses to glucagon in non-diabetic humans. Glucagon induced a transient increase in plasma insulin and C-peptide concentrations. At the dose level of 0.5 mg, glucagon elicited more efficient responses than at the dose level of 0.25 mg (p<0.05). However, the responses were not further potentiated by glucagon at 1.0 mg. Plasma glucose levels did not change during the first 2 min after glucagon injection, when already a marked increase in plasma insulin and C-peptide levels were observed. Thereafter, however, plasma glucose levels increased, to be maximal at 20 min after glucagon injection. Calculations of the minute-to-minute increase of plasma insulin and C-peptide levels revealed that plasma insulin levels increased by 32±7% of the increase in plasma C-peptide levels during the first 2 min, and by 36±6% of the increase in plasma C-peptide levels during the 3rd and 4th min after injection; the difference being the liver extraction of insulin. We conclude from this study in man 1) that glucagon stimulates insulin secretion through both direct and indirect effects, 2) that following glucagon injection, approximately 65% of the secreted insulin is extracted by the liver, and 3) that the dose level of 0.5 mg glucagon is the optimal dose level for the stimulation of insulin secration.