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| Content Provider | PubMed Central |
|---|---|
| Author | Sandström, Marie E. Zhang, Shi-jin Bruton, Joseph Silva, José P. Reid, Michael B. Westerblad, Håkan Katz, Abram |
| Copyright Year | 2006 |
| Abstract | Exercise increases glucose transport into skeletal muscle via a pathway that is poorly understood. We investigated the role of endogenously produced reactive oxygen species (ROS) in contraction-mediated glucose transport. Repeated contractions increased 2-deoxyglucose (2-DG) uptake roughly threefold in isolated, mouse extensor digitorum longus (fast-twitch) muscle. N-Acetylcysteine (NAC), a non-specific antioxidant, inhibited contraction-mediated 2-DG uptake by ∼50% (P < 0.05 versus control values), but did not significantly affect basal 2-DG uptake or the uptake induced by insulin, hypoxia or 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR, which mimics AMP-mediated activation of AMP-activated protein kinase, AMPK). Ebselen, a glutathione peroxidase mimetic, also inhibited contraction-mediated 2-DG uptake (by almost 60%, P < 0.001 versus control values). Muscles from mice overexpressing Mn2+-dependent superoxide dismutase, which catalyses H2O2 production from superoxide anions, exhibited a ∼25% higher rate of contraction-mediated 2-DG uptake versus muscles from wild-type control mice (P < 0.05). Exogenous H2O2 induced oxidative stress, as judged by an increase in the [GSSG]/[GSH + GSSG] (reduced glutathione + oxidized glutathione) ratio to 2.5 times control values, and this increase was substantially blocked by NAC. Similarly, NAC significantly attenuated contraction-mediated oxidative stress as judged by measurements of glutathione status and the intracellular ROS level with the fluorescent indicator 5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein (P < 0.05). Finally, contraction increased AMPK activity and phosphorylation ∼10-fold, and NAC blocked ∼50% of these changes. These data indicate that endogenously produced ROS, possibly H2O2 or its derivatives, play an important role in contraction-mediated activation of glucose transport in fast-twitch muscle. |
| Related Links | http://dx.doi.org/10.1113/jphysiol.2006.110601 |
| Ending Page | 262 |
| Page Count | 12 |
| Starting Page | 251 |
| File Format | |
| ISSN | 00223751 |
| e-ISSN | 14697793 |
| Journal | The Journal of Physiology |
| Issue Number | Pt 1 |
| Volume Number | 575 |
| Language | English |
| Publisher | Blackwell Science Inc |
| Publisher Date | 2006-08-15 |
| Access Restriction | Open |
| Rights Holder | Blackwell Science Inc |
| Subject Keyword | Physiology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Sports Science |
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