Insulin regulation of insulin-like growth factor-binding protein production in cultured HepG2 cells.
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.
Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905.
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CA
Conover
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PD
Lee
D000906:Antibodies / Q000494:pharmacology; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis*; D003470:Culture Media; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008113:Liver Neoplasms; D011863:Radioimmunoassay; D011972:Receptor, Insulin / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000906:Antibodies; D002352:Carrier Proteins; D003470:Culture Media; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin