To investigate factors responsible for altered insulin sensitivity in uremia, we studied 125I-insulin binding to erythrocytes in 20 uremic patients before and after dialysis. In uremic patients, predialysis binding was 50% lower in comparison with healthy controls (4.35 ± 1.79 vs. 9.37 ± 1.30%; p < 0.01). Five-hour dialysis treatment resulted in a rapid increase in binding (on average to 55%; p < 0.01). During the course of dialysis, binding to erythrocytes from 2 selected patients steadily increased in a time-dependent manner (on average 24%/h). The dialysis-induced increase in binding did not correlate with the changes in plasma insulin levels, but depended on the efficiency of dialysis as assessed by a relative decrease in plasma urea and creatinine. After an intravenous glucose load, the insulin-to-glucose ratio decreased in parallel with the increase in binding after dialysis. The results indicate that uremic plasma contains dialyzable substances which reversibly inhibit insulin binding, leading to altered insulin sensitivity.
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.
Insulin binding to specific erythrocyte receptors was investigated in group of 25 subjects with Klinefelter's syndrome (47 XXY genotype) and 14 healthy male volunteers. Insulin binding was significantly decreased in Klinefelter subjects (P less than 0.01 at insulin concentrations of 0.051 and 0.136 mmol/liter); however, their fasting glucose concentration was normal (87 +/- 17), and the glucose disappearance rate was slightly increased (2.3 +/- 0.9; P less than 0.2). These data indicated a compensatory, mechanism involved in the glucose metabolism in Klinefelter's syndrome.
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