IRS1 and Hyperinsulinemia: The dysregulation of insulin sensitivity in SF rats may occur at high concentration of H2O2, because hydrogen peroxide, in the presence of hyperinsulinemia, was reported to have a significant negative effect on insulin signaling and to cause a selective phosphorylation in serine/threonine and loss of IRS1 and 2 proteins which further inhibit insulin response in mammalian skeletal muscle [33, 34].