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Nox2 NADPH Oxidase Has a Critical Role in Insulin Resistance–Related Endothelial Cell Dysfunction
Insulin resistance is characterized by excessive endothelial cell generation of potentially cytotoxic concentrations of reactive oxygen species. We examined the role of NADPH oxidase (Nox) and specifically Nox2 isoform in superoxide generation in two complementary in vivo models of human insulin res...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661635/ https://www.ncbi.nlm.nih.gov/pubmed/23349484 http://dx.doi.org/10.2337/db12-1294 |
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author | Sukumar, Piruthivi Viswambharan, Hema Imrie, Helen Cubbon, Richard M. Yuldasheva, Nadira Gage, Matthew Galloway, Stacey Skromna, Anna Kandavelu, Parkavi Santos, Celio X. Gatenby, V. Kate Smith, Jessica Beech, David J. Wheatcroft, Stephen B. Channon, Keith M. Shah, Ajay M. Kearney, Mark T. |
author_facet | Sukumar, Piruthivi Viswambharan, Hema Imrie, Helen Cubbon, Richard M. Yuldasheva, Nadira Gage, Matthew Galloway, Stacey Skromna, Anna Kandavelu, Parkavi Santos, Celio X. Gatenby, V. Kate Smith, Jessica Beech, David J. Wheatcroft, Stephen B. Channon, Keith M. Shah, Ajay M. Kearney, Mark T. |
author_sort | Sukumar, Piruthivi |
collection | PubMed |
description | Insulin resistance is characterized by excessive endothelial cell generation of potentially cytotoxic concentrations of reactive oxygen species. We examined the role of NADPH oxidase (Nox) and specifically Nox2 isoform in superoxide generation in two complementary in vivo models of human insulin resistance (endothelial specific and whole body). Using three complementary methods to measure superoxide, we demonstrated higher levels of superoxide in insulin-resistant endothelial cells, which could be pharmacologically inhibited both acutely and chronically, using the Nox inhibitor gp91ds-tat. Similarly, insulin resistance–induced impairment of endothelial-mediated vasorelaxation could also be reversed using gp91ds-tat. siRNA-mediated knockdown of Nox2, which was specifically elevated in insulin-resistant endothelial cells, significantly reduced superoxide levels. Double transgenic mice with endothelial-specific insulin resistance and deletion of Nox2 showed reduced superoxide production and improved vascular function. This study identifies Nox2 as the central molecule in insulin resistance–mediated oxidative stress and vascular dysfunction. It also establishes pharmacological inhibition of Nox2 as a novel therapeutic target in insulin resistance–related vascular disease. |
format | Online Article Text |
id | pubmed-3661635 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-36616352014-06-01 Nox2 NADPH Oxidase Has a Critical Role in Insulin Resistance–Related Endothelial Cell Dysfunction Sukumar, Piruthivi Viswambharan, Hema Imrie, Helen Cubbon, Richard M. Yuldasheva, Nadira Gage, Matthew Galloway, Stacey Skromna, Anna Kandavelu, Parkavi Santos, Celio X. Gatenby, V. Kate Smith, Jessica Beech, David J. Wheatcroft, Stephen B. Channon, Keith M. Shah, Ajay M. Kearney, Mark T. Diabetes Original Research Insulin resistance is characterized by excessive endothelial cell generation of potentially cytotoxic concentrations of reactive oxygen species. We examined the role of NADPH oxidase (Nox) and specifically Nox2 isoform in superoxide generation in two complementary in vivo models of human insulin resistance (endothelial specific and whole body). Using three complementary methods to measure superoxide, we demonstrated higher levels of superoxide in insulin-resistant endothelial cells, which could be pharmacologically inhibited both acutely and chronically, using the Nox inhibitor gp91ds-tat. Similarly, insulin resistance–induced impairment of endothelial-mediated vasorelaxation could also be reversed using gp91ds-tat. siRNA-mediated knockdown of Nox2, which was specifically elevated in insulin-resistant endothelial cells, significantly reduced superoxide levels. Double transgenic mice with endothelial-specific insulin resistance and deletion of Nox2 showed reduced superoxide production and improved vascular function. This study identifies Nox2 as the central molecule in insulin resistance–mediated oxidative stress and vascular dysfunction. It also establishes pharmacological inhibition of Nox2 as a novel therapeutic target in insulin resistance–related vascular disease. American Diabetes Association 2013-06 2013-05-17 /pmc/articles/PMC3661635/ /pubmed/23349484 http://dx.doi.org/10.2337/db12-1294 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Original Research Sukumar, Piruthivi Viswambharan, Hema Imrie, Helen Cubbon, Richard M. Yuldasheva, Nadira Gage, Matthew Galloway, Stacey Skromna, Anna Kandavelu, Parkavi Santos, Celio X. Gatenby, V. Kate Smith, Jessica Beech, David J. Wheatcroft, Stephen B. Channon, Keith M. Shah, Ajay M. Kearney, Mark T. Nox2 NADPH Oxidase Has a Critical Role in Insulin Resistance–Related Endothelial Cell Dysfunction |
title | Nox2 NADPH Oxidase Has a Critical Role in Insulin Resistance–Related Endothelial Cell Dysfunction |
title_full | Nox2 NADPH Oxidase Has a Critical Role in Insulin Resistance–Related Endothelial Cell Dysfunction |
title_fullStr | Nox2 NADPH Oxidase Has a Critical Role in Insulin Resistance–Related Endothelial Cell Dysfunction |
title_full_unstemmed | Nox2 NADPH Oxidase Has a Critical Role in Insulin Resistance–Related Endothelial Cell Dysfunction |
title_short | Nox2 NADPH Oxidase Has a Critical Role in Insulin Resistance–Related Endothelial Cell Dysfunction |
title_sort | nox2 nadph oxidase has a critical role in insulin resistance–related endothelial cell dysfunction |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661635/ https://www.ncbi.nlm.nih.gov/pubmed/23349484 http://dx.doi.org/10.2337/db12-1294 |
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