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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

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
› Author Affiliations
Further Information

Publication History

received 10 December 2013

accepted 24 July 2014

Publication Date:
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

 

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