EVIDENCE FOR A ROLE OF INSULIN IN HEPATOCYTIC DIFFERENTIATION OF HUMAN HEPATOMA BC1 CELLS

To examine the effect of insulin on hepatocytic differentiation, we lo ok advantage of the properties of the newly established human hepatoma BC1 cell line to maintain quiescence after confluency and to progress ively acquire in culture (3 weeks after confluency) an hepatocytic phe notype, as assessed by expression of specific hepatic genes (Le Jossic ct al., 1995). In BC1 cells cultured in the presence of insulin (1 mu M), expression of albumin and transferrin mRNA and protein occurs ear lier than in tells cultured in its absence (1 week vs 2 weeks). Moreov er, at any time considered, the level of the two hepatic markers was h igher (2- to 3-fold) in the former than in untreated cells. The benefi cial effect of insulin on hepatocytic differentiation of BC1 cells was paralleled by: i) modest increases in insulin receptor (IR) mRNA leve l and IR binding activity, and ii) a 6-fold increase in sensitivity to insulin for stimulation of glycogenesis. These results provide the fi rst evidence for insulin's ability to exert a positive effect on hepat ocytic differentiation. The beneficial effect of insulin probably resu lts both from increased IR expression and binding activity and from al teration at post-receptor levels.