AKT1 and Hyperinsulinemia: Hyperinsulinemia, which is the result of insulin resistance, causes decreased activation of eNOS through an insulin receptor substrate (IRS)-1/phosphatidylinositol 3-kinase (PI3K) signaling/protein kinase B (Akt)-mediated pathway, a decrease in NO bioavailability, and a consequent increase in arterial stiffness [35].