Since the discovery of endothelin peptides in the mid-1980s by Yanigasawa and colleagues, accumulating evidence demonstrates that these peptides may function beyond vasoconstriction. Strong epidemiologic associations between insulin resistance and increased endothelin levels or activity have been found, and these associations have prompted studies investigating the interactions of endothelin with insulin. In this review we explore the evidence for such interactions at multiple levels of physiology, ranging from effects on tissue perfusion through modulation of vascular tone to subcellular interactions of endothelin signaling with insulin signaling. The evidence implicating endothelin in insulin resistance and its associated vascular and metabolic abnormalities is reviewed.
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