The very same unbalanced activity in this branch of insulin signaling allows compensatory hyperinsulinemia to overstimulate the unaffected mitogen activated protein (MAP)-kinase pathway, which contributes to trigger endothelial dysfunction by increasing endothelin-1 (ET-1) release, and set a proinflammatory predisposition to pro-thrombotic and pro-atherogenic vascular events [13,14]. This evidence concerns the gene EDN1 and endothelial dysfunction.