Diminished insulin receptors on monocytes and erythrocytes in hypertriglyceridemia

Carbohydrate intolerance is a common observation in endogenous hypertriglyceridemia (HL). So far the nature of this metabolic defect, which accompanies postprandial hyperinsulinemia and a reduced hypoglycemic action of insulin, has not been elucidated. We have examined cellular insulin binding in 20 subjects affected with HL (average plasma triglyceride level, 437 ± 311 mg/dL) to test the possibility that a receptor defect is involved in peripheral insulin resistance. Monocytes from the HL subjects bound, on the average, 34% less insulin than cells from eight normotriglyceridemic controls of comparable age and body weight (average plasma TG level, 169 ± 34 mg/dL). Likewise, erythrocytes from the HL group bound 29.6% less insulin than did those from control subjects. Scatchard analysis of the binding data revealed that the number of insulin receptors was reduced for both types of cells. To test if the abnormality in cellular insulin-binding capacity in these subjects is an inherent defect or secondary to the hypertriglyceridemia, 11 of the subjects participated in a 4-month training program (120 minutes weekly of moderate exercise at 60% Vo 2 max), while the remaining nine persons served as controls. Training reduced the average plasma TG level from 373 ± 270 to 277 ± 139 mg/dL ( P < 0.01), but cellular insulin binding was not significantly affected. In addition, no correlation was found between the individual TG plasma concentration and cellular insulin binding. Thus, training itself also proved ineffective in enhancing insulin binding, most probably due to exertion of insufficient intensity. It is concluded that the defective insulin action in endogenous hypertriglyceridemia is, at least to some degree, due to an abnormality at the receptor level. This abnormality may be primary or secondary to the disturbed carbohydrate utilization.