Decrease in insulin and insulin-like growth factor I (IGF-I) binding to erythrocytes from patients with cystic fibrosis.

Abstract

Cystic fibrosis, an autosomal recessive disease affecting exocrine glands, is associated in many cases with a severe undernutritional state, growth retardation and glucose intolerance. To obtain a better definition of the possible defects of insulin and insulin-like growth factor I (IGF-I) receptors, we investigated 125I-insulin and 125I-IGF-I binding to erythrocytes from patients with cystic fibrosis (n = 23) and controls (n = 13). Erythrocytes were isolated by Ficoll-Hypaque gradient centrifugation, and hormone binding was performed in cell suspensions of 3 x 10(9) cells/ml. Cystic fibrosis patients displayed a statistically significant 33% and 40% (p < 0.05) decrease of insulin and IGF-I binding, respectively, compared to controls. These alterations were due to an almost 50% reduction in the binding capacity of the high-affinity receptor compartment. Affinity constants were modified to a lesser extent, except for a two-fold decrease in K1 of the high-affinity compartment of insulin receptors. Interestingly, the decrease in insulin binding was proportional to the degree of growth failure. The statistical significance of hormone binding alterations was assessed in terms of the graphic distribution of individual affinity constants and binding capacity values. Although variable, 50 to 60% of cystic fibrosis patients displayed alterations in stoichiometric binding parameters located outside the area described by the 95% tolerance interval of controls. A major reduction in insulin and IGF-I binding in conditions of low and normal insulin and IGF-I plasma levels, respectively, as well as the correlation with the degree of growth failure in patients with cystic fibrosis, may contribute to an understanding of the pathogenesis of insulin resistance and glucose abnormalities in undernutritional states.