Insulin regulation of insulin-like growth factor-binding protein production in cultured HepG2 cells

J Clin Endocrinol Metab. 1990 Apr;70(4):1062-7. doi: 10.1210/jcem-70-4-1062.


A human hepatoma cell line, HepG2, secretes a discrete insulin-like growth factor-binding protein (IGFBP-1) into serum-free medium, which is identical to the 25K mol wt BP in amniotic fluid and plasma. IGFBP-1 levels in vivo have been shown to be inversely correlated with circulating insulin concentrations. This study investigated the direct effects of insulin on IGFBP-1 production in vitro. Addition of insulin to HepG2 cultures induced a rapid dose-dependent decrease in IGFBP-1 synthesis and secretion independent of the glucose concentration in the medium. As assessed by ligand binding and specific RIA, levels of IGFBP-1 were 20-50% of control levels in 18-h conditioned medium from insulin-treated cells. Monoclonal antibody studies indicated that the suppressive effect of insulin on IGFBP-1 synthesis was mediated through specific interaction with the insulin receptor. Therefore, HepG2 cells respond to insulin by altering the synthesis and secretion of IGFBP-1 in a manner that mimics many of the changes in plasma IGFBP-1 levels observed in vivo and provide an in vitro model for studies of IGFBP-1 biosynthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / pharmacology
  • Blotting, Western
  • Carcinoma, Hepatocellular / metabolism*
  • Carrier Proteins / biosynthesis*
  • Culture Media
  • Humans
  • Insulin / pharmacology*
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor I / metabolism
  • Liver Neoplasms
  • Radioimmunoassay
  • Receptor, Insulin / immunology
  • Receptor, Insulin / metabolism
  • Tumor Cells, Cultured / drug effects


  • Antibodies
  • Carrier Proteins
  • Culture Media
  • Insulin
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor I
  • Receptor, Insulin