Retraction. Direct evidence for downregulation of insulin receptors by physiologic hyperinsulinemia in man.

To directly examine whether physiologic hyperinsulinemia regulates insulin receptors in normal man, we studied the effect of insulin infusion (employing the euglycemic insulin clamp technique) on 125I-insulin binding to monocytes. In Study I (9 subjects), when the steady-state plasma insulin concentration was raised to approximately 100 muU/ml, insulin binding to monocytes remained unchanged at 1 h, but decreased significantly by 3 h (20%, P less than 0.01) and fell further by 5 h (37%, P less than 0.001) following the insulin infusion. In Study II (5 subjects) increments in plasma insulin concentration to 31 muU/ml resulted in no change in insulin binding at 3 h (P greater than 0.5) but resulted in a significant decrease at 5 h (25%, P less than 0.01). The plasma glucose concentration was maintained at basal levels in both infusion protocols. The decrease in insulin binding in both studies was due to a decrease in insulin receptor concentration. No significant change in receptor affinity was observed. In a control study (5 subjects) 5 h of saline infusion had no effect on insulin binding to monocytes. We conclude that in normal humans, increments in the plasma insulin concentration in the physiologic range downregulates the number of insulin receptors in a dose- and time-dependent manner.