Insulin-like growth factor-I serum concentrations and patterns of insulin-like growth factor binding proteins in patients with chronic liver disease

Abstract

Background/Aims: Serum concentrations of insulin-like growth factor-I are decreased in liver cirrhosis. However, this growth factor is bound for the most part to specific binding proteins that are known to modulate biological actions. Plasma insulin-like growth factor binding proteins are predominantly synthesized in the liver. Methods: The effect of liver disease on basal and on growth hormone-stimulated serum concentrations of total and “free” insulin-like growth factor-I and on insulin-like growth factor binding protein patterns is reported. Sera were obtained from 20 patients with non-cirrhotic chronic liver diseases and from 20 patients with cirrhosis before and 24 h after a single subcutaneous dose of growth hormone. Samples were analyzed using radioimmunoassays, gel chromatography, ligand blotting and immunoblotting. Results: In cirrhosis, serum concentrations of total and “free” insulin-like growth factor-I were decreased, the binding protein pattern was changed profoundly showing a reduction in the 150 kD complex and an increase in the 30–40 kD complexes. Concentrations of binding protein-1 and -2 were increased, while that of binding protein-3 was decreased in cirrhosis. The response to growth hormone was blunted. These changes were related to the degree of liver dysfunction as assessed by the Child-Pugh classification. Conclusions: A pathogenetic link of altered bioavailability of insulin-like growth factor-I to clinical characteristics of advanced liver disease, e.g. insulin resistance or skeletal muscle wasting, may be suggested by the present data.