Mitochondrial antioxidative capacity regulates muscle glucose uptake in the conscious mouse: effect of exercise and diet

Li Kang, Mary E. Lustig, Jeffrey S. Bonner, Robert S. Lee-Young, Wesley H. Mayes, Freyja D. James, Chien-Te Lin, Christopher G. R. Perry, Ethan J. Anderson, P. Darrell Neufer, David H Wasserman

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


The objective of this study was to test the hypothesis that exercise-stimulated muscle glucose uptake (MGU) is augmented by increasing mitochondrial reactive oxygen species (mtROS) scavenging capacity. This hypothesis was tested in genetically altered mice fed chow or a high-fat (HF) diet that accelerates mtROS formation. Mice overexpressing SOD2 (sod2(Tg)), mitochondria-targeted catalase (mcat(Tg)), and combined SOD2 and mCAT (mtAO) were used to increase mtROS scavenging. mtROS was assessed by the H(2)O(2) emitting potential (JH(2)O(2)) in muscle fibers. sod2(Tg) did not decrease JH(2)O(2) in chow-fed mice, but decreased JH(2)O(2) in HF-fed mice. mcat(Tg) and mtAO decreased JH(2)O(2) in both chow- and HF-fed mice. In parallel, the ratio of reduced to oxidized glutathione (GSH/GSSG) was unaltered in sod2(Tg) in chow-fed mice, but was increased in HF-fed sod2(Tg) and both chow- and HF-fed mcat(Tg) and mtAO. Nitrotyrosine, a marker of NO-dependent, reactive nitrogen species (RNS)-induced nitrative stress, was decreased in both chow- and HF-fed sod2(Tg), mcat(Tg), and mtAO mice. This effect was not changed with exercise. Kg, an index of MGU was assessed using 2-[(14)C]-deoxyglucose during exercise. In chow-fed mice, sod2(Tg), mcat(Tg), and mtAO increased exercise Kg compared with wild types. Exercise Kg was also augmented in HF-fed sod2(Tg) and mcat(Tg) mice but unchanged in HF-fed mtAO mice. In conclusion, mtROS scavenging is a key regulator of exercise-mediated MGU and this regulation depends on nutritional state.

Original languageEnglish
Pages (from-to)1173-1183
Number of pages11
JournalJournal of Applied Physiology
Issue number8
Early online date15 Oct 2012
Publication statusPublished - Oct 2012


  • Action Potentials/physiology
  • Animal Feed
  • Animals
  • Antioxidants/metabolism
  • Biological Transport/physiology
  • Catalase/metabolism
  • Diet, High-Fat
  • Glucose/metabolism
  • Glutathione Disulfide/metabolism
  • Hydrogen Peroxide/metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic/metabolism
  • Mitochondria/metabolism
  • Muscle, Skeletal/metabolism
  • Nitric Oxide/metabolism
  • Physical Conditioning, Animal/physiology
  • Reactive Nitrogen Species/metabolism
  • Reactive Oxygen Species/metabolism
  • Superoxide Dismutase/metabolism
  • Tyrosine/analogs & derivatives


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