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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
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.
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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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