| Autor: |
Li Kang, Chunhua Dai, Lustig, Mary E., Bonner, Jeffrey S., Mayes, Wesley H., Mokshagundam, Shilpa, James, Freyja D., Thompson, Courtney S., Chien-Te Lin, Perry, Christopher G. R., Anderson, Ethan J., Neufer, P. Darrell, Wasserman, David H., Powers, Alvin C. |
| Předmět: |
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| Zdroj: |
Diabetes; Nov2014, Vol. 63 Issue 11, p3699-3710, 12p, 1 Chart, 7 Graphs |
| Abstrakt: |
Elevated reactive oxygen species (ROS) are linked to insulin resistance and islet dysfunction. Manganese superoxide dismutase (SOD2) is a primary defense against mitochondrial oxidative stress. To test the hypothesis that heterozygous SOD2 deletion impairs glucose-stimulated insulin secretion (GSIS) and insulin action, wild-type (sod2+/+) and heterozygous knockout mice (sod2+/-) were fed a chow or high-fat (HF) diet, which accelerates ROS production. Hyperglycemic (HG) and hyperinsulinemic-euglycemic (HI) clamps were performed to assess GSIS and insulin action in vivo. GSIS during HG clamps was equal in chow-fed sod2+/- and sod2+/+ but was markedly decreased in HF-fed sod2+/-. Remarkably, this impairment was not paralleled by reduced HG glucose infusion rate (GIR). Decreased GSIS in HF-fed sod2+/- was associated with increased ROS, such as superoxide ion. Surprisingly, insulin action determined by HI clamps did not differ between sod2+/- and sod2+/+ of either diet. Since insulin action was unaffected, we hypothesized that the unchanged HG GIR in HF-fed sod2+/- was due to increased glucose effectiveness. Increased GLUT-1, hexokinase II, and phospho-AMPK protein in muscle of HF-fed sod2+/- support this hypothesis. We conclude that heterozygous SOD2 deletion in mice, a model that mimics SOD2 changes observed in diabetic humans, impairs GSIS in HF-fed mice without affecting insulin action. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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