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Open Access
Horm Metab Res 2014; 46(11): 749-752
DOI: 10.1055/s-0034-1387701
Hypothesis
© Georg Thieme Verlag KG Stuttgart · New York

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

Autor*innen

  • I. A. Szijártó

    1   2nd Department of Medicine and Nephrological Center, University of Pécs, Pécs, Hungary
    2   Experimental and Clinical Research Center (ECRC), Max Delbrück Center for Molecular Medicine, Berlin, Germany
    3   Medical Clinic for Nephrology and Internal Intensive Care, Charité Campus Virchow Klinikum, Berlin, Germany
    4   Interdisziplinäres Stoffwechsel-Centrum, Charité, Campus Virchow Klinikum, Berlin, Germany

  • G. A. Molnár

    1   2nd Department of Medicine and Nephrological Center, University of Pécs, Pécs, Hungary

  • E. Mikolás

    1   2nd Department of Medicine and Nephrological Center, University of Pécs, Pécs, Hungary

  • V. Fisi

    1   2nd Department of Medicine and Nephrological Center, University of Pécs, Pécs, Hungary

  • J. Cseh

    1   2nd Department of Medicine and Nephrological Center, University of Pécs, Pécs, Hungary

  • B. Laczy

    1   2nd Department of Medicine and Nephrological Center, University of Pécs, Pécs, Hungary

  • T. Kovács

    1   2nd Department of Medicine and Nephrological Center, University of Pécs, Pécs, Hungary

  • K. Böddi

    5   Department of Biochemistry and Medical Chemistry, University of Pécs, Pécs, Hungary

  • A. Takátsy

    5   Department of Biochemistry and Medical Chemistry, University of Pécs, Pécs, Hungary

  • M. Gollasch

    2   Experimental and Clinical Research Center (ECRC), Max Delbrück Center for Molecular Medicine, Berlin, Germany
    3   Medical Clinic for Nephrology and Internal Intensive Care, Charité Campus Virchow Klinikum, Berlin, Germany

  • A. Koller

    6   Department of Pathophysiology and Gerontology and Szentágothai Research Centre University of Pécs, Hungary
    7   Department of Physiology, New York Medical College, Valhalla, NY, USA
    8   Department of Pathophysiology, Semmelweis University, Budapest, Hungary

  • I. Wittmann

    1   2nd Department of Medicine and Nephrological Center, University of Pécs, Pécs, Hungary
Weitere Informationen

Publikationsverlauf

received 10. Dezember 2013

accepted 24. Juli 2014

Publikationsdatum:
10. September 2014 (online)

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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.

Key words

insulin - vasomotor function - ortho-tyrosine - eNOS

Supporting Information