EDN1 and endothelial dysfunction: Physiological levels of insulin promote NO production, through insulin-like growth factor-1 (IGF-1) PI3K/Akt-related pathways to promote eNOS activity in endothelial cells [19], whereas insulin resistance induces endothelial dysfunction in mesenteric vessels, characterized by impaired PI3K and enhanced mitogen-activated protein kinase- (MAPK-) dependent ET-1 secretion [20].