Downregulation of insulin receptors in obese man.

In an attempt to determine whether the decreased number of insulin's receptors in obesity is a result of downregulation of the receptors, diazoxide (5 mg/kg/d) was given to 10 obese subjects. Insulin's suppression by diazoxide in these 10 subjects resulted in a mild glucose intolerance and an increase in insulin's receptors in seven of the 10 subjects. The subjects could be divided into three groups by analyzing the Scatchard plots of their insulin receptor studies before and after diazoxide. Four subjects exhibited an increase in both high affinity and low affinity receptors, three showed an increase only in high affinity receptors, and three failed to demonstrate any change in receptors in response to diazoxide. These studies support the concept that the decreased number of insulin's receptors observed in obesity is a result of the downregulation of the receptors and is not the primary, underlying cause of insulin resistance in obesity, although a contributory role cannot be ruled out.