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: I A Szijártó, G A Molnár, E Mikolás, V Fisi, J Cseh, B Laczy, T Kovács, K Böddi, A Takátsy, M Gollasch, A Koller, I Wittmann
• Journal: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme (Horm Metab Res) Vol. 46 Issue 11 Pg. 749-52 (Oct 2014) ISSN: 1439-4286 [Electronic] Germany
• PMID: 25208272 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Georg Thieme Verlag KG Stuttgart · New York.

Chemical References

• Insulin
• Tyrosine
• 2-tyrosine
• Nitric Oxide Synthase Type III

Topics

• Administration, Oral
• Animals
• Cells, Cultured
• Endothelial Cells (drug effects, metabolism)
• Endothelium, Vascular (drug effects, metabolism)
• Femoral Artery (drug effects, physiology)
• In Vitro Techniques
• Insulin (pharmacology)
• Male
• Mice
• Nitric Oxide Synthase Type III (metabolism)
• Phosphorylation (drug effects)
• Rats, Sprague-Dawley
• Tyrosine (metabolism)
• Vasodilation (drug effects)