Defect in insulin binding to receptors in obese man. Amelioration with calorie restriction

of [JI]insulin in vitro to circulating lymphocytes from 11 obese patients was less than that observed with cells from 10 thin volunteers. Furthermore, with obese cells, unlabeled insulin was less effective in competing with labeled hormone for binding, both at low and high con-centrations of unlabeled insulin. These differences were not accounted for by the high concentrations of insulin in the circulation of the obese patients at the time the blood was drawn, or by differences in degradation of hormone, or in the characteristics of the cell population. The decrease in binding appears to be due to a lowering of the receptor concentration, but some loss of affinity has not been excluded. Institution of a calorie re-stricted diet (nine patients) which ameliorated the hy-perinsulinemia, produced an improvement in hormone binding. Since the insulin receptors of lymphocytes in metabolic disorders seem to reflect the state of insulin receptors in target cells such as liver and fat, the lym-phocytes or other leukocytes appear to be ideal for studies of impaired cell responsiveness to hormones in man