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Genetic Disruption of SOD1 Gene Causes Glucose Intolerance and Impairs β-Cell Function
Oxidative stress has been associated with insulin resistance and type 2 diabetes. However, it is not clear whether oxidative damage is a cause or a consequence of the metabolic abnormalities present in diabetic subjects. The goal of this study was to determine whether inducing oxidative damage throu...
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/PMC3837066/ https://www.ncbi.nlm.nih.gov/pubmed/24009256 http://dx.doi.org/10.2337/db13-0314 |
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author | Muscogiuri, Giovanna Salmon, Adam B. Aguayo-Mazzucato, Cristina Li, Mengyao Balas, Bogdan Guardado-Mendoza, Rodolfo Giaccari, Andrea Reddick, Robert L. Reyna, Sara M. Weir, Gordon DeFronzo, Ralph A. Van Remmen, Holly Musi, Nicolas |
author_facet | Muscogiuri, Giovanna Salmon, Adam B. Aguayo-Mazzucato, Cristina Li, Mengyao Balas, Bogdan Guardado-Mendoza, Rodolfo Giaccari, Andrea Reddick, Robert L. Reyna, Sara M. Weir, Gordon DeFronzo, Ralph A. Van Remmen, Holly Musi, Nicolas |
author_sort | Muscogiuri, Giovanna |
collection | PubMed |
description | Oxidative stress has been associated with insulin resistance and type 2 diabetes. However, it is not clear whether oxidative damage is a cause or a consequence of the metabolic abnormalities present in diabetic subjects. The goal of this study was to determine whether inducing oxidative damage through genetic ablation of superoxide dismutase 1 (SOD1) leads to abnormalities in glucose homeostasis. We studied SOD1-null mice and wild-type (WT) littermates. Glucose tolerance was evaluated with intraperitoneal glucose tolerance tests. Peripheral and hepatic insulin sensitivity was quantitated with the euglycemic-hyperinsulinemic clamp. β-Cell function was determined with the hyperglycemic clamp and morphometric analysis of pancreatic islets. Genetic ablation of SOD1 caused glucose intolerance, which was associated with reduced in vivo β-cell insulin secretion and decreased β-cell volume. Peripheral and hepatic insulin sensitivity were not significantly altered in SOD1-null mice. High-fat diet caused glucose intolerance in WT mice but did not further worsen the glucose intolerance observed in standard chow–fed SOD1-null mice. Our findings suggest that oxidative stress per se does not play a major role in the pathogenesis of insulin resistance and demonstrate that oxidative stress caused by SOD1 ablation leads to glucose intolerance secondary to β-cell dysfunction. |
format | Online Article Text |
id | pubmed-3837066 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-38370662014-12-01 Genetic Disruption of SOD1 Gene Causes Glucose Intolerance and Impairs β-Cell Function Muscogiuri, Giovanna Salmon, Adam B. Aguayo-Mazzucato, Cristina Li, Mengyao Balas, Bogdan Guardado-Mendoza, Rodolfo Giaccari, Andrea Reddick, Robert L. Reyna, Sara M. Weir, Gordon DeFronzo, Ralph A. Van Remmen, Holly Musi, Nicolas Diabetes Original Research Oxidative stress has been associated with insulin resistance and type 2 diabetes. However, it is not clear whether oxidative damage is a cause or a consequence of the metabolic abnormalities present in diabetic subjects. The goal of this study was to determine whether inducing oxidative damage through genetic ablation of superoxide dismutase 1 (SOD1) leads to abnormalities in glucose homeostasis. We studied SOD1-null mice and wild-type (WT) littermates. Glucose tolerance was evaluated with intraperitoneal glucose tolerance tests. Peripheral and hepatic insulin sensitivity was quantitated with the euglycemic-hyperinsulinemic clamp. β-Cell function was determined with the hyperglycemic clamp and morphometric analysis of pancreatic islets. Genetic ablation of SOD1 caused glucose intolerance, which was associated with reduced in vivo β-cell insulin secretion and decreased β-cell volume. Peripheral and hepatic insulin sensitivity were not significantly altered in SOD1-null mice. High-fat diet caused glucose intolerance in WT mice but did not further worsen the glucose intolerance observed in standard chow–fed SOD1-null mice. Our findings suggest that oxidative stress per se does not play a major role in the pathogenesis of insulin resistance and demonstrate that oxidative stress caused by SOD1 ablation leads to glucose intolerance secondary to β-cell dysfunction. American Diabetes Association 2013-12 2013-11-16 /pmc/articles/PMC3837066/ /pubmed/24009256 http://dx.doi.org/10.2337/db13-0314 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 Muscogiuri, Giovanna Salmon, Adam B. Aguayo-Mazzucato, Cristina Li, Mengyao Balas, Bogdan Guardado-Mendoza, Rodolfo Giaccari, Andrea Reddick, Robert L. Reyna, Sara M. Weir, Gordon DeFronzo, Ralph A. Van Remmen, Holly Musi, Nicolas Genetic Disruption of SOD1 Gene Causes Glucose Intolerance and Impairs β-Cell Function |
title | Genetic Disruption of SOD1 Gene Causes Glucose Intolerance and Impairs β-Cell Function |
title_full | Genetic Disruption of SOD1 Gene Causes Glucose Intolerance and Impairs β-Cell Function |
title_fullStr | Genetic Disruption of SOD1 Gene Causes Glucose Intolerance and Impairs β-Cell Function |
title_full_unstemmed | Genetic Disruption of SOD1 Gene Causes Glucose Intolerance and Impairs β-Cell Function |
title_short | Genetic Disruption of SOD1 Gene Causes Glucose Intolerance and Impairs β-Cell Function |
title_sort | genetic disruption of sod1 gene causes glucose intolerance and impairs β-cell function |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837066/ https://www.ncbi.nlm.nih.gov/pubmed/24009256 http://dx.doi.org/10.2337/db13-0314 |
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