School of Medicine Publications and Presentations
Document Type
Article
Publication Date
12-2013
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. 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.
Recommended Citation
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 β-cell function. Diabetes, 62(12), 4201–4207. https://doi.org/10.2337/db13-0314
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Publication Title
Diabetes
DOI
10.2337/db13-0314
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
Copyright 2013 by the American Diabetes Association