Suppression of insulin secretion by C-peptide infusion in humans.

A role for insulin in the regulation of its own secretion has been established; however, no such effect of C-peptide has been demonstrated. In order to reexamine the role of C-peptide and insulin in regulating beta cell secretion, we infused C-peptide as a primed continuous infusion of 1 ng/min per kg for 45 min to 7 healthy volunteers, and insulin in a similar manner at rates of 1 and 10 mU/min per kg for 2 h to 14 healthy subjects using the euglycemic insulin clamp technique. Plasma insulin and C-peptide were measured before and during the infusions. During C-peptide infusion, C-peptide levels rose from 1.8 +/- 0.2 to 2.3 +/- 0.2 ng/ml, and insulin levels fell from 14.5 +/- 0.8 to 11.0 +/- 1.0 microU/ml (P < 0.01). During low and high rate insulin infusions, insulin levels rose to 70 +/- 8 and 1,020 +/- 105 microU/ml, while C-peptide levels fell significantly from 1.9 +/- 0.2 to 1.5 +/- 0.2 and to 1.3 +/- 0.1 ng/ml, respectively. Thus 5- and 70-fold increases in circulating insulin levels caused 15% and 33% drops in serum C-peptide, respectively. However, a 30% increase in C-peptide levels caused a significant approximately 24% decrease in the levels of plasma insulin. We conclude that insulin induces a dose-dependent inhibition of beta cell secretion, which is even more sensitive to inhibition by C-peptide. These data suggest a physiological role for C-peptide in regulating human insulin secretion in vivo.