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.