EDN1 and metabolic syndrome: On the one hand, the insulin-mediated activation of the phosphoinositide 3-kinase pathway is decreased, while activation of the extracellular signal-regulated protein kinase 1/2 and the production of endothelin-1 by insulin are normal.23 On the other hand, it has been found that cholesterol homeostasis is related with insulin secretory, and dyslipidemia causes defects in insulin secretion and alterations of glucose metabolism.