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Role of reactive oxygen species in contraction‐mediated glucose transport in mouse skeletal muscle
Author(s) -
Sandström Marie E.,
Zhang ShiJin,
Bruton Joseph,
Silva José P.,
Reid Michael B.,
Westerblad Håkan,
Katz Abram
Publication year - 2006
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.110601
Subject(s) - glutathione , reactive oxygen species , chemistry , skeletal muscle , oxidative stress , ampk , medicine , endocrinology , glucose uptake , contraction (grammar) , glutathione peroxidase , superoxide , oxidative phosphorylation , glucose transporter , superoxide dismutase , antioxidant , biochemistry , protein kinase a , phosphorylation , insulin , biology , enzyme
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 Mn 2+ ‐dependent superoxide dismutase, which catalyses H 2 O 2 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 H 2 O 2 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 H 2 O 2 or its derivatives, play an important role in contraction‐mediated activation of glucose transport in fast‐twitch muscle.