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Insulin Regulation of Insulin-Like Growth Factor-Binding Protein Production in Cultured HepG2 Cells^*

Endocrine Research Unit, Mayo Clinic Rochester, Minnesota 55905
The Diabetes Research Center, Baylor College of Medicine Houston, Texas 77054

Address all correspondence and requests for reprints to: Dr. Cheryl Conover, Endocrine Research Unit, Room 5–164 West Joseph Building, Mayo Clinic, Rochester, Minnesota 55905.

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.

^* This work was supported in part by the Mayo Foundation (to C.A.C.) and a feasibility grant from the American Diabetes Association with funds contributed by the Colorado chapter of the American Diabetes Association (to P.D.K.L.).

Received August 14, 1989.

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