For instance, Catalano [57] reported that a strong and transient phosphorylation of INSR (almost immediately upon insulin addition), ERK (at 5 min), and AKT (at 10 min) in rat hepatoma cells in response to all insulin concentrations (5 × 10− 9, 1.7 × 10− 8, 1.7 × 10− 7 M), followed by a very rapid decline of INRS and ERK phosphorylation at 45 min and no declines in AKT autophosphorylation even 120 min after insulin addition, the total INSR, ERK and AKT protein levels were unchanged. This evidence concerns the gene INS and hepatocellular carcinoma.