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Reduction in Mn‐superoxide dismutase (SOD2) corrects insulin resistance due to high fat feeding in oxidative tissues of mice
Author(s) -
Conniff Mary Elizabeth,
James Freyja D,
Huang TingTing,
Wasserman David H
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1226.44
Subject(s) - sod2 , medicine , endocrinology , insulin , superoxide dismutase , insulin resistance , chemistry , glucose transporter , superoxide , oxidative stress , glucose uptake , biochemistry , enzyme
SOD2 is a mitochondrial antioxidant enzyme responsible for converting superoxide radical to H 2 O 2. Certain levels of H 2 O 2 are essential while excessive levels are harmful to normal metabolic function. We hypothesized that reducing the formation of H 2 O 2 by decreasing SOD2 expression by 50% would improve metabolic function. SOD2 +/− mice and wild type (WT) littermates (n=14/13) were chow or high fat fed (HF) for 3 months. Catheters were placed in the jugular vein and carotid artery. 5 days later a hyperinsulinemic glucose clamp was performed. 2‐deoxyglucose was given for analysis of tissue glucose uptake. Body weight, 5 h fasted blood glucose or insulin levels were not different between SOD2 +/− and WT on either diet. Glucose infusion rate (mg/kg/min) to maintain euglycemia was similar in SOD2 +/− and WT on chow (49±4 vs 49±6) and HF (32±3 vs 35±4). The rates of glucose uptake (R g ; μmol/100g tissue /min) in vastus lateralis muscle were not different between SOD2 +/− and WT on either diet. Heart R g was significantly higher in SOD2 +/− compared to WT (174±9 vs 130±13) but there was no difference in diaphragm R g (46±19 vs 46±8) on chow. WT mice on HF had impaired insulin stimulated glucose uptake in heart (71±9) and diaphragm (22 ± 3). Heart R g (167±26) and diaphragm R g (157±12) were not impaired by HF in SOD2 +/− . A 50% reduction in SOD2 activity corrects the HF induced insulin resistance that occurs in highly oxidative tissues, such as diaphragm and heart. Supported by DK 54902 and DK 59637