Here we have investigated insulin-driven PI3K and RAS-MAPK signaling, gluconeogenic gene expression, glucose production, and fatty acid synthase (FAS) protein levels in primary mouse hepatocytes and in three hepatoma cell lines from three different species: human HepG2; mouse Hepa 1–6 cells; and rat McARH7777. The gene discussed is FASN; the disease is hepatocellular carcinoma.