DIVERGENT EFFECTS OF PHORBOL ESTERS AND INSULIN ON INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-1 (IGFBP-1) PRODUCTION AND MESSENGER-RNA IN RAT H4IIE HEPATOMA-CELLS

125I-IGF-I binding assay, western ligand and immunoblotting, and northern analysis of total RNA reveal that phorbol ester agonists of protein kinase C rapidly enhance IGFBP-1 production and increase the abundance of IGFBP-1 mRNA in rat H4IIE hepatoma cells. In combination with insulin, a potent inhibitor of IGFBP-1 gene transcription, this early effect of phorbol esters is dominant. These results demonstrate divergent regulation of IGFBP-1 by phorbol esters and insulin and indicate that protein kinase C may play a critical role in the regulation of IGFBP-1 and modulation IGF bioactivity in metabolic disease. © 1992 Academic Press, Inc.