The effect of glucocorticoid on 125I-insulin binding to human erythrocytes Possible postreceptor modulation of receptor binding

Abstract

To evaluate the role of insulin receptors in the pathogenesis of insulin resistance observed in glucocorticoid excess, we measured 125I-insulin binding to circulating erythrocytes in 7 patients with Cushing's syndrome and 7 patients with adrenal insufficiency. Insulin receptor binding was higher in Cushing's syndrome and was lower in adrenal insufficiency, compared to normal subjects. Insulin binding decreased after transsphenoidal surgery in 2 patients with Cushing's syndrome. In addition, glucocorticoid treatment in 6 patients with adrenal insufficiency resulted in the increase of insulin binding. The biological significance of this phenomenon must await further investigation, but it does suggest that insulin resistance in glucocorticoid excess should be interpreted as an alteration of cellular mechanisms of insulin at a step distal to the insulin receptor. Increased insulin binding to the receptor is probably modulated by postreceptor events.