Lack of Insulin Feedback Inhibition in Nonobese and Obese Men

The existence of insulin feedback inhibition is a controversial issue. The present study adopted a novel approach to determine whether insulin feedback inhibition exists in vivo during physiologic hyperinsulinemia and if it could contribute to enhanced insulin secretion in obesity. Serial plasma insulin and C-peptide levels were determined during a basal state and a hyperinsulinemic clamp (287 pmol/min/m2) and following discontinuation of the insulin infusion under euglycemic conditions. Insulin secretion rates were derived from plasma C-peptide levels and individual C-peptide kinetics using a two-compartment model. Eight non-obese and nine obese men were recruited for the studies, which were performed in random order. Men with significant variations in glucose levels during hyperinsulinemia were excluded from the analysis. Plasma glucose levels were similar between the non-obese and obese groups during all phases of the study, and similar plasma insulin levels were achieved in both groups during euglycemic hyperinsulinemia. In obese men, C-peptide levels were significantly greater compared with non-obese men during euglycemic hyperinsulinemia (P < .05). However, neither the non-obese nor the obese group demonstrated significant suppression of insulin secretion rates during euglycemic hyperinsulinemia. Expressing the data in absolute terms or as a percent of basal did not alter the results. Moreover, there was no significant change between the non-obese and the obese group during the rapid onset and cessation of hyperinsulinemia. Under euglycemic conditions, physiologic hyperinsulinemia does not induce suppression of endogenous insulin secretion in non-obese or obese men.