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.

The Effect of Guanidino Substances from Uremic Plasma on Insulin Binding to Erythrocyte Receptors in Uremia

“…Our previous studies demonstrated the strong inhibitory effect of uremic plasma on insulin binding of normal erythrocytes (Milutinovic et al 1983). The cross-incubation experiments with progressive dilution of uremic plasma revealed a parallel decrease in degree of inhibition, what suggested the presence of a humoral inhibitor(s) of insulin binding in uremic plasma.…”

Changes in Insulin Binding during Hemodialysis in Uremic Patients

“…In a recent report [13], we demonstrated in cross-incu bation studies with uremic plasma and control erythro cytes the presence of an inhibitor of insulin binding in plasma of uremic patients. In this article we extend our investigations to follow the changes of insulin binding in uremic patients in response to a gradual decrease in concentration of uremic toxins occurring during hemodi alysis.…”

“…In a recent study [13], we reproduced the acute modifications of insulin binding in uremia and after hemodialysis in vitro by incubating red cells (normal and uremic) with uremic and normal plasma. Incubation of normal erythrocytes with uremic plasma resulted in 60% decrease in specific insulin binding and the inhibition could be reversed by reincubation of uremic red cells with control plasma.…”