Heterozygous SOD2 Deletion Impairs Glucose-Stimulated Insulin Secretion, but Not Insulin Action, in High-Fat–Fed Mice
| Autor: | Jeffrey S. Bonner, Wesley H. Mayes, Shilpa Mokshagundam, P. Darrell Neufer, Freyja D. James, Chunhua Dai, Courtney S. Thompson, Ethan J. Anderson, Mary E. Lustig, Li Kang, Christopher G. R. Perry, David H. Wasserman, Alvin C. Powers, Chien-Te Lin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism medicine.medical_treatment Blotting Western SOD2 Biology medicine.disease_cause Diet High-Fat Superoxide dismutase chemistry.chemical_compound Mice Insulin resistance Superoxides Internal medicine Internal Medicine medicine Animals Insulin skin and connective tissue diseases Muscle Skeletal chemistry.chemical_classification Reactive oxygen species geography geography.geographical_feature_category Superoxide Reverse Transcriptase Polymerase Chain Reaction Superoxide Dismutase medicine.disease Islet Mice Mutant Strains Oxidative Stress Endocrinology Metabolism Glucose chemistry biology.protein cardiovascular system Reactive Oxygen Species Oxidative stress |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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