Receptor Mediated Insulin Degradation Decreased by Chloroquine in Isolated Rat Adipocytes

Abstract

The time-course of insulin binding to isolated adipocytes pretreated with chloroquine (0.1mM) showed that no steady state condition was reached and that the binding kept increasing with the time of incubation up to three hours. Sixty-one percent of the bound labeled insulin could not be dissociated from these cells by 100 μg/ml of unlabeled insulin, whereas 86% dissociated from the control cells. Chromatography revealed that the bound intact insulin, which had the ability to bind to insulin receptors of adipocytes, was increased and that degraded insulin decreased in the chloroquine treated cells. However, these cells showed normal insulin stimulation of 2-deoxy-glucose uptake. The data suggest that insulin is internalized in adipocytes after binding to insulin receptors and that insulin is degraded at the site, probably lysosomes, where chloroquine inhibits this degradation process.