Insulin Suppresses Its Own Secretion In Vivo

Abstract

This study addressed the controversial question of whether a negative—insulin-feedback loop exists in vivo. We utilized prehepatic insulin production, calculated by computerized deconvolution analysis of peripheral C-peptide concentration, as a measure of endogenous insulin secretion. Prehepatic insulin production was determined in 10 normal men who randomly underwent a control study and two additional studies involving different insulin infusion rates that achieved circulating insulin concentrations within the physiologic range during euglycemic clamps. The results demonstrate a dose-dependent suppression of prehepatic insulin production from 5.8 ± 1.4 mU/min during the control study to 4.0 ± 1.2 and 3.2 ± 0.9 mU/min during plasma insulin levels of 34 ± 4 and 61 ± 6 μU/ml, respectively (P < .05). Therefore, in contrast to recently reported results in vitro, insulin inhibits its own secretion in humans.