Disulfide reduction converts the insulin receptor of human placenta to a low affinity form

Abstract

Treatment of human placenta membranes with diothiothietol (DTT) followed by N-ethylmaleimide results in a 60% reduction in insulin binding. Treatment with N-ethylmaleimide alone has little effect. The decrease in insulin binding that results from DTT treatment is due to a decrease in affinity for insulin, with little change in total receptor number. DTT has similar effects on receptor solubilized from placenta membranes with Triton X-100, indicating that its effects are not attributable to changes in the arrangement of receptors in the membrane. In contrast to placenta treatment of liver membranes with DDT does not decrease insulin landing. These results suggest that reduction of a critical disulfide bond in insulin receptors from human placenta converts the receptor to a low affinity form.