Rac1 – a novel regulator of contraction‐stimulated glucose uptake in skeletal muscle. Issue 12 (20th October 2014)

• Record Type: Journal Article
• Authors: Sylow, Lykke; Møller, Lisbeth L. V.; Kleinert, Maximilian; Richter, Erik A.; Jensen, Thomas E.
• Is Part Of: Experimental physiology. Volume 99:Issue 12(2014:Dec.)
• Page Start: 1574
• Page End: 1580
• Publication Date: 2014-10-20
• Subjects: Physiology, Experimental -- Periodicals; 571.0724
• DOI: 10.1113/expphysiol.2014.079194
• Languages: English
• ISSNs: 0958-0670

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="eph1537-sec-0010" sec-type="section"> <title>New Findings</title> <p> <list id="eph1537-list-0001" list-type="bullet"> <list-item> <p> <bold>What is the topic of this review?</bold> </p> <p>Novel evidence indicates a role of the GTPase Rac1 in the regulation of exercise‐ and contraction‐stimulated glucose uptake in skeletal muscle.</p> </list-item> <list-item> <p> <bold>What advances does it highlight?</bold> </p> <p>The intracellular mechanisms regulating exercise and contraction‐stimulated glucose uptake in muscle are not well understood. Recent findings from our group suggest that Rac1 is an important regulator of contraction‐stimulated glucose uptake. In this review, we discuss published and unpublished findings supporting a role of Rac1 in exercise/contraction‐stimulated glucose uptake. The possible downstream effectors of Rac1 are also considered.</p> </list-item> </list> </p> </sec> <sec id="eph1537-sec-0020" sec-type="section"> <p>Muscle contraction stimulates muscle glucose uptake by facilitating translocation of glucose transporter 4 from intracellular locations to the cell surface, which allows for diffusion of glucose into the myofibres. The intracellular mechanisms regulating this process are not well understood. The GTPase Rac1 has, until recently, been investigated only with regard to its involvement in insulin‐stimulated glucose uptake. However, we recently found that Rac1 is activated during muscle contraction and exercise in mice and humans. Remarkably, Rac1 seems to be necessary for exercise and contraction‐stimulated glucose uptake in skeletal muscle, because muscle‐specific Rac1 knockout mice display reduced <italic>ex vivo</italic> contraction‐ and <italic>in vivo</italic> exercise‐stimulated glucose uptake. The molecular mechanism by which Rac1 regulates glucose uptake is presently unknown. However, recent studies link Rac1 to the actin cytoskeleton, the small GTPase RalA and/or free radical production, which have previously been shown to be regulators of glucose uptake in muscle. We propose a model in which Rac1 is activated by contraction‐ and exercise‐induced mechanical stress signals and that Rac1 in conjunction with other signalling regulates glucose uptake during muscle contraction and exercise.</p> </sec> </abstract>