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Hyperuricemia-induced endothelial insulin resistance: the nitric oxide connection.

Hyperuricemia-induced endothelial insulin resistance: the nitric oxide connection.

Authors :
Bahadoran Z
Mirmiran P
Kashfi K
Ghasemi A
Source :
Pflugers Archiv : European journal of physiology [Pflugers Arch] 2022 Jan; Vol. 474 (1), pp. 83-98. Date of Electronic Publication: 2021 Jul 27.
Publication Year :
2022

Abstract

Hyperuricemia, defined as elevated serum concentrations of uric acid (UA) above 416 µmol L <superscript>-1</superscript> , is related to the development of cardiometabolic disorders, probably via induction of endothelial dysfunction. Hyperuricemia causes endothelial dysfunction via induction of cell apoptosis, oxidative stress, and inflammation; however, it's interfering with insulin signaling and decreased endothelial nitric oxide (NO) availability, resulting in the development of endothelial insulin resistance, which seems to be a major underlying mechanism for hyperuricemia-induced endothelial dysfunction. Here, we elaborate on how hyperuricemia induces endothelial insulin resistance through the disruption of insulin-stimulated endothelial NO synthesis. High UA concentrations decrease insulin-induced NO synthesis within the endothelial cells by interfering with insulin signaling at either the receptor or post-receptor levels (i.e., proximal and distal steps). At the proximal post-receptor level, UA impairs the function of the insulin receptor substrate (IRS) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) in the insulin signaling pathway. At the distal level, high UA concentrations impair endothelial NO synthase (eNOS)-NO system by decreasing eNOS expression and activity as well as by direct inactivation of NO. Clinically, UA-induced endothelial insulin resistance is translated into impaired endothelial function, impaired NO-dependent vasodilation, and the development of systemic insulin resistance. UA-lowering drugs may improve endothelial function in subjects with hyperuricemia.<br /> (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Details

Language :
English
ISSN :
1432-2013
Volume :
474
Issue :
1
Database :
MEDLINE
Journal :
Pflugers Archiv : European journal of physiology
Publication Type :
Academic Journal
Accession number :
34313822
Full Text :
https://doi.org/10.1007/s00424-021-02606-2