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

Treatment of human placenta membranes with dithiothrietol (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 membranes, treatment of liver membranes with DTT does not decrease insulin binding. These results suggest that reduction of a critical disulfide bond in insulin receptors from human placenta converts the receptor to a low affinity form.