Short-term Regulation of Insulin Receptor Affinity in Man

Publisher Website
Google Scholar
Abstract
We have studied the short term regulation of insulin receptors by serially measuring insulin binding to erythrocytes during 5 h of infusions of glucose and insulin. Two infusion protocols were employed: (1) Hyperinsulinemic study. Subjects were infused with insulin (80 mU/min) to induce sustained hyperinsulinemia, while euglycemia was approximated by infusion of glucose (8 mg/kg/min). (2) Hyperglycemic study. Subjects were infused with glucose (7 mg/kg/min) and a small amount of insulin (10 mU/min), while endogenous insulin secretion was inhibited with epinephrine and propranolol. Insulin binding to erythrocyte insulin receptors was measured serially during both of these infusion protocols for 5 h. The results demonstrated no change in insulin binding during the first 3 h of either infusion. However, by 5 h of either infusion, a striking 36% decrease in insulin binding, from 6.3 ± 0.5% to 4.0 ± 0.6%, was observed. Scatchard analysis and average affinity analysis of the binding data demonstrated that this decrease in insulin binding was entirely caused by a decrease in receptor affinity. Insulin binding to circulating monocytes was also measured, and comparable effects were observed. When cells were removed from the in vivo environment at 3 h and were incubated in vitro for a subsequent 2 h, decreased insulin binding developed during the incubation. Thus, this short term regulation of insulin receptor affinity occurred in vivo or in vitro, and cells that were programmed during the first 3 h of the infusion study could develop a decrease in insulin receptor affinity in vitro in the absence of plasma factors.