Insulin-receptor turnover and down regulation in hepatocytes

Receptor-mediated degradation of 125I-insulin by hepatocytes was studied to evaluate its role in down-regulation of insulin receptors in liver. The amount of 125I-insulin bound to the cell surface was found to remain relatively constant during times of active insulin degradation over a wide range of insulin concentrations, even in the presence of cycloheximide. This observation, as well as other considerations discussed in the text, suggest that down-regulation of insulin receptors is not an inevitable consequence of receptor-mediated degradation in insulin, but rather represents a distinct metabolic effect of the hormone.