SUPPRESSION OF INSULIN-SECRETION BY C-PEPTIDE INFUSION IN HUMANS

A role for insulin in the regulation of its own secretion has been est ablished; however, no such effect of C-peptide has been demonstrated. In order to reexamine the role of C-peptide and insulin in regulating a 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 hea lthy subjects using the euglycemic insulin clamp technique. Plasma ins ulin and C-peptide were measured before and during the infusions. Duri ng 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 mu U/m l (P <0.01). During low and high rate insulin infusions, insulin level s rose to 70+/-8 and 1,020+/-105 mu U/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, resp ectively. 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 similar to 24% d ecrease in the levels of plasma insulin. We conclude that insulin indu ces a dose-dependent inhibition of beta cell secretion, which is even more sensitive to inhibition by C-peptide. These data suggest a physio logical role for C-peptide in regulating human insulin secretion in vi vo.