FLUCTUATIONS IN AFFINITY AND CONCENTRATION OF INSULIN RECEPTORS ON CIRCULATING MONOCYTES OF OBESE PATIENTS - EFFECTS OF STARVATION, REFEEDING, AND DIETING

The binding of 125I-insulin to insulin receptors on circulating monocytes of obese patients and normal volunteers was determined under various dietary states. In the basal, fed state the monocytes of obese patients with clinical insulin resistance (n = 6) bound less insulin than normals (n = 10) because of a decrease in insulin receptor concentration (obese = 6000-13,000 sites/monocyte vs. normals 15,000-28,000 sites/monocyte). The single obese patient without evidence of clinical insulin resistance demonstrated normal binding of insulin with 16,000 sites/monocyte. In all patients the total receptor concentration was inversely related to the circulating levels of insulin measured at rest after an overnight fast. For the obese patients with basally depressed insulin binding, a 48-72 h fast lowered circulating insulin and increased binding to normal levels but only at low hormone concentrations; this limited normalization of 125I-insulin binding was associated with increased receptor affinity for insulin without change in receptor concentration. Refeeding after the acute fasting periods resulted in return to the elevated plasma insulin levels, the basal receptor affinity and the depressed insulin binding observed in the basal, fed state. Chronic diet restored plasma insulin levels, insulin binding, and receptor concentration to normal without change in affinity. The insulin receptor of human monocytes is probably more sensitive to regulation by ambient insulin than the receptors of obese mice and cultured human lymphocytes. An insulin receptor undergoes in vivo modulation of its interaction with insulin by changing receptor concentration and by altering the affinity of existing receptors.