NYMC Faculty Publications

Elevated Vascular Level of Ortho-Tyrosine Contributes to the Impairment of Insulin-Induced Arterial Relaxation

Author Type(s)

Faculty

DOI

10.1055/s-0034-1387701

Journal Title

Hormone and Metabolic Research

First Page

749

Last Page

752

Document Type

Article

Publication Date

10-1-2014

Department

Medicine

Keywords

Administration, Oral, Animals, Cells, Cultured, Endothelial Cells, Endothelium, Vascular, Femoral Artery, In Vitro Techniques, Insulin, Male, Mice, Nitric Oxide Synthase Type III, Phosphorylation, Rats, Sprague-Dawley, Tyrosine, Vasodilation

Disciplines

Medicine and Health Sciences

Abstract

Previous studies have shown that in diabetes mellitus, insulin-induced relaxation of arteries is impaired and the level of ortho-tyrosine (o-Tyr), an oxidized amino acid is increased. Thus, we hypothesized that elevated vascular level of o-Tyr contributes to the impairment of insulin-induced vascular relaxation. Rats were fed with o-Tyr for 4 weeks. Insulin-induced vasomotor responses of isolated femoral artery were studied using wire myography. Vascular o-Tyr content was measured by HPLC, whereas immunoblot analyses were preformed to detect eNOS phosphorylation. Sustained oral supplementation of rats with o-Tyr increased the content of o-Tyr in the arterial wall and significantly reduced the relaxations to insulin. Sustained supplementation of cultured endothelial cells with o-Tyr increased the incorporation of o-Tyr and mitigated eNOS Ser (1 177) phosphorylation to insulin. Increasing arterial wall o-Tyr level attenuates insulin-induced relaxation - at least in part - by decreasing eNOS activation. Elevated level of o-Tyr could be an underlying mechanism for vasomotor dysfunction in diabetes mellitus.

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