Anti-insulin receptor antibody and insulin resistance

Abstract

Type B insulin resistance syndrome is characterized by the presence of a circulating anti-insulin receptor antibody which inhibits insulin action. The syndrome is usually associated with autoimmune diseases, acanthosis nigricans and hyperinsulinemia. The antibody causes insulin resistance by inhibiting insulin binding to insulin receptors, decreasing insulin receptor number, i.e. down regulation of insulin receptors, and desensitizing insulin receptors which leads to decreased insulin signal transduction through insulin receptors. It also has the ability to elicit insulin action associated with or without increased autophosphorylation of insulin receptors. The antibody usually binds to the insulin receptor with decreased association rate and decreased dissociation rate. The antibody which elicits insulin action without activation of kinase activity of insulin receptors may induce conformational change of insulin receptors. These characteristic features of the anti-insulin receptor antibody may be informative in solving the mechanism of insulin action and may be a useful tool to study insulin receptor functions.