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Erythrocyte Insulin Receptors in Chronic Renal Failure

Chronic renal failure is associated with altered insulin sensitivity of unclear etiology. To investigate the effect of renal failure on insulin binding, we studied insulin binding in mature erythrocyt

Insulin receptor defect in diabetic man with chronic renal failure: A comparison of erythrocyte insulin binding in diabetic and nondiabetic patients on maintenance hemodialysis

Abstract 125I-Insulin binding to most accessible and easily obtained circulating erythrocytes in 7 diabetic and 16 nondiabetic, nonobese patients with chronic renal failure (CRF) on maintenance hemodialysis was studied and compared with that of the 30 normal, nonobese volunteers. The percent-age of 125I-insulin binding was 4.7 ± 1.8 (mean ± SD) in the diabetic and 13.1 ± 2.4 in the nondiabetic patients with CRF while in the normal subjects it was 9.9 ± 1.4. There was no statistical difference in the fasting levels of glucose, insulin, and glycosylated hemoglobins in all the subjects studied. No correlation (r = −0.32) between insulin binding and endogenous insulin was observed in these subjects. The diabetic patients with CRF had no circulating factor(s) that would reduce insulin binding to normal erythrocytes. In comparison to the normal subjects, the reduction in insulin binding in the diabetic patients with CRF was accompanied by 47% reduction in insulin receptor sites (R0) but with no change in insulin receptor affinity, ( K e , 0.46 × 108 m −1), while in the nondiabetic patients with CRF no change in insulin receptor sites (R0) of increased affinity ( K e , 0.63 × 108 m −1) was observed. These findings suggest that insulin binding utilizing the much simpler erythrocyte insulin receptor assay can be used to evaluate alteration in insulin receptor status in CRF. These investigations also provide a very useful assay and characteristic studies for insulin receptors, if receptor modulation acquires a status of treatment for diabetes.

Acetylcholinesterase activity in chronic renal failure

Twenty healthy subjects and 39 Chronic Renal Failure patients (CRF-patients) maintained on chronic hemodialysis were used in this investigation to study the changes in acetylcholinesterase (AChE) activity of red blood cells (RBCs). The CRF-patients were all undergoing hemodialysis treatment. AChE activity from the CRF-patients was determined before and after dialysis. An additional objective was to study the effect of chronic renal failure on human red blood cell aging. Blood samples were drawn from controls and CRF-patients in tubes containing EDTA or sodium heparin as an anticoagulant. Red blood cells were purified to avoid interference with monocytes, reticulocytes and leukocytes. The purified RBCs were subfractionated into young (y) (1.08-1.09), mid (m) (1.09-1.11) and old (o) (1.11-1.12) percoll density (g/mL) fractions using a discontinous percoll gradient. The mean +/- SD AChE per gram hemoglobin (U/g Hgb) activities in whole blood (WB), purified human red blood cells (PRBCs), young human red blood cells (y-RBCs), mid age human red blood cells (m-RBCs) and old human red blood cells (o-RBCs) in CRF-patients were 31.2+/-3.43, 29.3+/-3.26, 30.4+/-3.91, 25.1+/-5.25, 17.1+/-6.02 in females and 29.8+/-5.39, 28.8+/-5.29, 28.7+/-5.29, 23.7+/-5.39 and 16.0+/-5.60 in males. AChE activity from CRF-patients were higher than that found in the control subjects. The aging of human RBCs in both the controls and CRF-patients showed a progressive reduction in AChE activity. AChE activity of RBCs from female CRF-patients were significantly higher (p < 0.05) than that of the female control subjects. The RBCs isolated from male CRF-patients showed a higher AChE activity than control males, but a significant difference was only observed with the mid-age-cells. These studies further indicate that AChE activity remained insignificantly different in the various density based age subfractions of RBCs of both CRF-patients and controls.

Metabolism of Insulin in Erythrocytes from Renal Failure Patients on Maintenance Hemodialysis

Glucose tolerance does not improve to the normal level after dialysis; however, our studies showed that the insulin receptor binding to erythrocytes of nondiabetic patients with chronic renal failure (CRF) on hemodialysis was more than that in normal subjects. To understand this apparent anomaly in insulin receptor action and glucose metabolism, we investigated insulin degradation-a postreceptor event of insulin binding-in erythrocytes from CRF patients and compared it with that of normal subjects. We studied insulin degradation by erythrocytes from each of eight CRF patients and five normal subjects. The average hyperbolic insulin degradation curve for the CRF patients showed lower activity and a right-handed shift compared to the curve for the normal subjects. The average maximum degradation of insulin in the CRF patients was significantly lower than that of normal subjects. The number of erythrocytes required to produce 50% of maximum insulin degradation was significantly greater in these patients than that in the normal subjects. Furthermore, a linear correlation was observed between the duration of dialysis and maximum percent of insulin degradation in the CRF patients. Clinical implications of these findings are unclear at the present time. However, the insulin-degrading activity in erythrocytes may be reflective of that in other body tissues.