Prolonged hyperglycemia and hyperinsulinemia-developed insulin resistance in HepG2 cells strongly triggered the overexpression of G6PC and Foxo1, by opposition to healthy cells (p < 0.001), denoting the excessive gluconeogenesis within IR hepatocytes, and the resulting de novo synthesis of glucose, which has been identified as one of the major causes of hyperglycaemia in the course of type 2 diabetes. This evidence concerns the gene FOXO1 and Hyperinsulinemia.