title: Skeletal Muscle Vascular Function: A Counterbalance of Insulin Action.
abstract: Insulin is a vasoactive hormone that regulates vascular homeostasis by maintaining balance of endothelial-derived NO and ET-1. Although there is general agreement that insulin resistance and the associated hyperinsulinemia disturb this balance, the vascular consequences for hyperinsulinemia in isolation from insulin resistance are still unclear. Presently, there is no simple answer for this question, especially in a background of mixed reports examining the effects of experimental hyperinsulinemia on endothelial-mediated vasodilation. Understanding the mechanisms by which hyperinsulinemia induces vascular dysfunction is essential in advancing treatment and prevention of insulin resistance-related vascular complications. Thus, we review literature addressing the effects of hyperinsulinemia on vascular function. Furthermore, we give special attention to the vasoregulatory effects of hyperinsulinemia on skeletal muscle, the largest insulin-dependent organ in the body. This review also characterizes the differential vascular effects of hyperinsulinemia on large conduit vessels versus small resistance microvessels and the effects of metabolic variables in an effort to unravel potential sources of discrepancies in the literature. At the cellular level, we provide an overview of insulin signaling events governing vascular tone. Finally, we hypothesize a role for hyperinsulinemia and insulin resistance in the development of CVD.
authors.affiliation: Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, Illinois, USA.|Integrative Physiology Laboratory, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Abeer M
authors.initials: AM
authors.lastname: Mahmoud
authors.affiliation: Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, Illinois, USA.|Integrative Physiology Laboratory, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Brown
authors.affiliation: Integrative Physiology Laboratory, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, Illinois, USA.|Department of Physical Therapy, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Shane A
authors.initials: SA
authors.lastname: Phillips
authors.affiliation: Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, Illinois, USA.|Integrative Physiology Laboratory, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Haus
mesh_terms: D000818:Animals; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D014652:Vascular Diseases / Q000378:metabolism / Q000503:physiopathology
chemical_list: D007328:Insulin; D009569:Nitric Oxide
keywords: hyperinsulinemia; insulin resistance; skeletal muscle; vascular dysfunction