In order to clarify the pathogenesis of glucose intolerance in chronic renal failure, we investigated it from the viewpoint of insulin receptor. IV-GTT (0.5g/kg) was performed in 10 undialyzed and 12 dialyzed patients with chronic renal failure and 6 normal subjects, and their insulin receptors were examined. ∑IRI (the sum of IRI during IV-GTT) in the undialyzed group was 445±78μU/m
l, which was significantly higher than that (260±38μU/m
l) in the normal group. The K value (glucose disappearance rate) in the undialyzed group was 1.32±0.30, which was significantly lower than that (1.92±0.25) in the normal group and that (1.82±0.34) in the dialyzed group. No significant difference in K value was recognized between the normal and dialyzed groups.
The specific binding of
125I-insulin to erythrocytes (2.4×10
9 cells/m
l) in the undialyzed group was 3.99±0.76% which was significantly lower than that (5.50±0.69%) in the normal group. However, no significant difference was observed between the normal and dialyzed groups. When competition data for the three groups were subjected to Scatchard analysis, the difference in binding to erythrocytes appeared to be due to the difference in receptor concentration rather than receptor affinity (receptor concentration: 42, 58, and 64 sites/erythrocyte in the undialyzed, dialyzed, and normal groups, respectively). In the dialyzed group, the correlation coefficients between the specific binding of
125I-insulin and K value (r=0.542) were higher than those between the binding and fasting IRI, ∑IRI (r=-0.381, -0.272).
From these results, it is suggested that glucose intolerance in chronic renal failure is founded on a decrease in insulin receptor concentration, and that hemodialysis improves this glucose intolerance through increased sensitivity to insulin action in the peripheral tissue with accompanying normalization of the insulin receptors.
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