Genetic disruption of sod1 gene causes glucose intolerance and impairs b-cell function

Giovanna Muscogiuri, Adam B. Salmon, Cristina Aguayo-Mazzucato, Mengyao Li, Bogdan Balas, Rodolfo Guardado-Mendoza, Andrea Giaccari, Robert L. Reddick, Sara M. Reyna, Gordon Weir, Ralph A. DeFronzo, Holly Van Remmen, Nicolas Musi

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18 Scopus citations

Abstract

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. b-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 b-cell insulin secretion and decreased b-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 b-cell dysfunction.

Original languageEnglish (US)
Pages (from-to)4201-4207
Number of pages7
JournalDiabetes
Volume62
Issue number12
DOIs
StatePublished - Dec 1 2013

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Muscogiuri, G., Salmon, A. B., Aguayo-Mazzucato, C., Li, M., Balas, B., Guardado-Mendoza, R., Giaccari, A., Reddick, R. L., Reyna, S. M., Weir, G., DeFronzo, R. A., Van Remmen, H., & Musi, N. (2013). Genetic disruption of sod1 gene causes glucose intolerance and impairs b-cell function. Diabetes, 62(12), 4201-4207. https://doi.org/10.2337/db13-0314