PHYSIOLOGICAL CONCENTRATION OF AMINO-ACIDS REGULATES INSULIN-LIKE-GROWTH-FACTOR-BINDING PROTEIN-1 EXPRESSION

Protein undernutrition is characterized by growth failure in young gro wing animals. Current evidence suggests that biosynthesis of insulin-l ike growth factor (IGF)-I and IGF-binding protein 1 (IGFBP-1) are key control points for nutritional regulation of growth. Here we examined the role of amino acid limitation in regulating the IGFBP-1 expression in the hepatic cell line. Our data show that leucine limitation stron gly induces IGFBP-1 without affecting IGF-I and IGF-II expression in h uman HepG2 cells and in isolated rat hepatocytes. Depletion of arginin e, cystine and all essential amino acids leads to induction of IGFBP-1 mRNA and protein expression in a dose-dependent manner. IGFBP-1 expre ssion is significantly induced by leucine concentration in the range o f that observed in the blood of rats fed a low-protein diet or in huma ns affected by kwashiorkor. Moreover, treatment of HepG2 cells with am ino acids at a concentration reproducing the amino acid concentration found in portal blood of rats fed a low-protein diet leads to a signif icantly higher expression of IGFBP-1. These data represent the first d emonstration that an amino acid limitation, as occurs during dietary p rotein deficiency, induces IGFBP-1 expression in hepatic cells. Theref ore, amino acids by themselves can play, in concert with hormones, an important role in the control of gene expression.