EDN1 and Hyperinsulinemia: Furthermore, assessment of effects of hypo- and hyperinsulinemia on vascular reactivity via nitric oxide and insulin signaling proteins such as Akt and endothelial nitric oxide synthase combined with altered plasma levels of endothelin-1, asymmetric dimethylarginine and nitric oxide may elucidate mechanisms behind sevoflurane-induced MBF changes in diabetic patients[38-41].