TY - JOUR

T1 - Rac1- a novel regulator of contraction-stimulated glucose uptake in skeletal muscle

AU - Sylow, Lykke

AU - Møller, Lisbeth L V

AU - Kleinert, Maximilian

AU - Richter, Erik A.

AU - Jensen, Thomas Elbenhardt

N1 - CURIS 2014 NEXS 307

PY - 2014

Y1 - 2014

N2 - Muscle contraction stimulates muscle glucose uptake by facilitating translocation of the glucose transporter 4 from intracellular locations to the cell surface, which allows for diffusion of glucose into the myofibers. However, the intracellular mechanisms regulating this process are not well understood. The GTPase, Rac1 has, until recently, only been investigated with regards 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/contraction-stimulated glucose uptake in skeletal muscle, since muscle-specific Rac1 knockout mice display reduced ex vivo contraction- and in vivo exercise-stimulated glucose uptake in skeletal muscle. The molecular mechanisms by which Rac1 regulate 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 stretch signals and that Rac1 in conjunction with other signaling regulates glucose uptake during muscle contraction and exercise. This article is protected by copyright. All rights reserved.

AB - Muscle contraction stimulates muscle glucose uptake by facilitating translocation of the glucose transporter 4 from intracellular locations to the cell surface, which allows for diffusion of glucose into the myofibers. However, the intracellular mechanisms regulating this process are not well understood. The GTPase, Rac1 has, until recently, only been investigated with regards 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/contraction-stimulated glucose uptake in skeletal muscle, since muscle-specific Rac1 knockout mice display reduced ex vivo contraction- and in vivo exercise-stimulated glucose uptake in skeletal muscle. The molecular mechanisms by which Rac1 regulate 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 stretch signals and that Rac1 in conjunction with other signaling regulates glucose uptake during muscle contraction and exercise. This article is protected by copyright. All rights reserved.

U2 - 10.1113/expphysiol.2014.079194

DO - 10.1113/expphysiol.2014.079194

M3 - Journal article

C2 - 25239922

VL - 99

SP - 1574

EP - 1580

JO - Experimental Physiology

JF - Experimental Physiology

SN - 0958-0670

IS - 12

ER -