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.
Original language | English |
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Pages (from-to) | 4201-4207 |
Number of pages | 7 |
Journal | Diabetes |
Volume | 62 |
DOIs | |
Publication status | Published - 2013 |
Keywords
- Animals
- Blood Glucose
- Diet, High-Fat
- Glucose Intolerance
- Glucose Tolerance Test
- Insulin
- Insulin Resistance
- Insulin-Secreting Cells
- Mice, Knockout
- Oxidative Stress
- Superoxide Dismutase
- cellule secernenti insulina
- dieta iperlipidica
- insulina
- insulino-resistenza
- metabolismo glucidico
- modello animale
- stress ossidativo
- superossido dismutasi
- test di tolleranza glucidica
- tolleranza glucidica