The administration of endothelin-1 (ET-1), a vasoconstrictor, leads to insulin resistance, as characterized by a decrease in IRS-1 protein levels and suppressed PI3K/Akt activation in rat skeletal muscle (Wilkes et al., 2003) and adipocytes (Ishibashi et al., 2001), further promoting increased vasoconstriction and atherogenesis. The gene discussed is AKT1; the disease is Insulin resistance.