Furthermore, ET-1 can directly interfere with cellular insulin signaling (38–42), enhance hepatic glucose output (43), diminish glucose uptake (40, 44–47), impair insulin secretion (48) and stimulate lipolysis in adipose tissue (39, 49) – effects directly contributing to hyperglycemia and development of type 2 diabetes. This evidence concerns the gene EDN1 and type 2 diabetes mellitus.