Inhibitor of insulin binding to erythrocytes in plasma of uremic patients.

Abstract

Previously, we have shown that insulin binding (IB) to erythrocytes was decreased in uremic patients and that hemodialysis corrected the receptor defect. In the present study cross-incubation experiments were performed using uremic and control erythrocytes and plasma. Incubation of control erythrocytes with uremic plasma resulted in a 60% decrease in specific insulin binding, and progressive dilutions of uremic plasma revealed a parallel decrease in degree of inhibition suggesting the presence of an inhibitor of insulin binding in uremic plasma. Plasma obtained from uremic patients exhibiting lower IB to their erythrocytes was more potent in inhibition of IB to control erythrocytes, i.e. predialysis in comparison with postdialysis plasma. The alteration of IB was reversible since incubation of uremic erythrocytes with normal plasma restored IB towards normal values. Subjects having higher IB to their erythrocytes had more efficient plasma in restoring IB to uremic erythrocytes. The data indicate that alteration of insulin binding in uremia is mediated by dialysable plasma inhibitors. The possibility that humoral factors affecting binding of insulin to its receptors can in this way influence the sensitivity of peripheral tissues to insulin is considered.