| First Author | Muscogiuri G | Year | 2013 |
| Journal | Diabetes | Volume | 62 |
| Issue | 12 | Pages | 4201-7 |
| PubMed ID | 24009256 | Mgi Jnum | J:208922 |
| Mgi Id | MGI:5565397 | Doi | 10.2337/db13-0314 |
| Citation | Muscogiuri G, et al. (2013) Genetic disruption of SOD1 gene causes glucose intolerance and impairs beta-cell function. Diabetes 62(12):4201-7 |
| abstractText | 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. beta-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 beta-cell insulin secretion and decreased beta-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 beta-cell dysfunction. |
