NOS3 and Hyperinsulinemia: In the endothelium, a selective resistance to insulin is observed in the pathological state of hyperinsulinemia [8, 9], when the PI3K/AKT/eNOS pathway is altered, resulting in diminished eNOS activity, reduced NO generation and diminished insulin-mediated vasodilation; by contrast, the Ras/Raf/MAPK pathway is generally preserved, thus ET-1 production and mitogenic effects persist contributing to the vascular effects of insulin resistance [10].