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Para-Tyrosine Supplementation Improves Insulin- and Liraglutide- Induced Vasorelaxation in Cholesterol-Fed Rats

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Former data of our workgroup indicated that the accumulation of oxidized amino acids (meta- and ortho-tyrosine) due to oxidative stress may play an important role in the impaired insulininduced vasoactive properties of different arterial segments. There are evidences, that incorporation of these amino acids into cellular proteins leads to certain hormonal resistances, which might be restored by supplementation with the physiologic isoform, para-tyrosine.

Rats in the control group were kept on a regular diet, rats in the cholesterol-fed group received high-fat diet, while the third group of rats received high-fat diet with para-tyrosine supplementation for 16 weeks. Plasma cholesterol level was significantly higher in the cholesterol-fed group, while the level of cholesterol in the cholesterol+para-tyrosine group did not differ significantly from that of the controls. Plasma level of insulin after glucose stimulation was decreased in the cholesterol-fed group, while that in the para-tyrosine supplemented group did not differ significantly from the controls. Vascular para-, meta- and ortho-tyrosine content was measured with HPLC. Elevated vascular meta-tyrosine/para-tyrosine ratio of cholesterol fed rats could be avoided by para-tyrosine supplementation. Vascular response of the thoracic aorta to insulin and liraglutide was assessed by a DMT multi-myograph. Cholesterol feeding resulted in vascular insulin-and liraglutide resistance, which was restored by para-tyrosine supplementation.

Incorporation of the oxidative stress induced pathological tyrosine isoforms leads to vascular-hormone-resistances. We show that the physiological amino acid para-tyrosine is capable of restoring hypercholesterolemia-induced increased meta-tyrosine content of the vascular wall, thus attenuating functional vascular damage.
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Keywords: hormone resistance; oxidative stress; para-tyrosine

Document Type: Research Article

Publication date: August 1, 2015

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  • Protein & Peptide Letters publishes short papers in all important aspects of protein and peptide research, including structural studies, recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, drug design etc. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallisation, and preliminary structure determinations of biologically important proteins are acceptable. Purely theoretical papers are also acceptable provided they provide new insight into the principles of protein/peptide structure and function.
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