Role of reactive oxygen species in contraction-mediated glucose transport in mouse skeletal muscle.

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 approximately 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-beta-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 approximately 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 approximately 10-fold, and NAC blocked approximately 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.

• Authors: Marie E Sandström, Shi-Jin Zhang, Joseph Bruton, José P Silva, Michael B Reid, Håkan Westerblad, Abram Katz
• Journal: The Journal of physiology (J Physiol) Vol. 575 Issue Pt 1 Pg. 251-62 (Aug 15 2006) ISSN: 0022-3751 [Print] England
• PMID: 16777943 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Multienzyme Complexes
• Reactive Oxygen Species
• Deoxyglucose
• Hydrogen Peroxide
• Superoxide Dismutase
• superoxide dismutase 2
• Protein Serine-Threonine Kinases
• AMP-Activated Protein Kinases
• Glutathione
• Glucose
• Acetylcysteine

Topics

• AMP-Activated Protein Kinases
• Acetylcysteine (pharmacology)
• Animals
• Antioxidants (pharmacology)
• Deoxyglucose (metabolism)
• Glucose (metabolism)
• Glutathione (metabolism)
• Hydrogen Peroxide (pharmacology)
• In Vitro Techniques
• Male
• Mice
• Mice, Transgenic
• Multienzyme Complexes (metabolism)
• Muscle Contraction
• Muscle, Skeletal (drug effects, enzymology, physiology)
• Oxidative Stress
• Protein Serine-Threonine Kinases (metabolism)
• Reactive Oxygen Species (metabolism)
• Superoxide Dismutase (genetics, metabolism)