title: Elevated vascular level of ortho-tyrosine contributes to the impairment of insulin-induced arterial relaxation.
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.
authors.affiliation: 2nd Department of Medicine and Nephrological Center, University of Pécs, Pécs, Hungary.
authors.forename: I A
authors.initials: IA
authors.lastname: Szijártó
authors.affiliation: 2nd Department of Medicine and Nephrological Center, University of Pécs, Pécs, Hungary.
authors.forename: G A
authors.initials: GA
authors.lastname: Molnár
authors.affiliation: 2nd Department of Medicine and Nephrological Center, University of Pécs, Pécs, Hungary.
authors.forename: E
authors.initials: E
authors.lastname: Mikolás
authors.affiliation: 2nd Department of Medicine and Nephrological Center, University of Pécs, Pécs, Hungary.
authors.forename: V
authors.initials: V
authors.lastname: Fisi
authors.affiliation: 2nd Department of Medicine and Nephrological Center, University of Pécs, Pécs, Hungary.
authors.forename: J
authors.initials: J
authors.lastname: Cseh
authors.affiliation: 2nd Department of Medicine and Nephrological Center, University of Pécs, Pécs, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Laczy
authors.affiliation: 2nd Department of Medicine and Nephrological Center, University of Pécs, Pécs, Hungary.
authors.forename: T
authors.initials: T
authors.lastname: Kovács
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pécs, Pécs, Hungary.
authors.forename: K
authors.initials: K
authors.lastname: Böddi
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pécs, Pécs, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Takátsy
authors.affiliation: Experimental and Clinical Research Center (ECRC), Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Gollasch
authors.affiliation: Department of Pathophysiology and Gerontology and Szentágothai Research Centre University of Pécs, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Koller
authors.affiliation: 2nd Department of Medicine and Nephrological Center, University of Pécs, Pécs, Hungary.
authors.forename: I
authors.initials: I
authors.lastname: Wittmann
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D007328:Insulin; D014443:Tyrosine; C026741:2-tyrosine; D052250:Nitric Oxide Synthase Type III