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

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

AU - Jensen, Thomas Elbenhardt

N1 - CURIS 2014 NEXS 307

PY - 2014/12/1

Y1 - 2014/12/1

N2 - New Findings: What is the topic of this review? Novel evidence indicates a role of the GTPase Rac1 in the regulation of exercise- and contraction-stimulated glucose uptake in skeletal muscle. What advances does it highlight? 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 In this review, we discuss published and unpublished findings supporting a role of Rac1 in exercise/contraction-stimulated glucose uptake.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. 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 ex vivo contraction- and in vivo 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.

AB - New Findings: What is the topic of this review? Novel evidence indicates a role of the GTPase Rac1 in the regulation of exercise- and contraction-stimulated glucose uptake in skeletal muscle. What advances does it highlight? 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. 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 ex vivo contraction- and in vivo 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.

U2 - 10.1113/expphysiol.2014.079194

DO - 10.1113/expphysiol.2014.079194

M3 - Journal article

C2 - 25239922

SN - 0958-0670

VL - 99

SP - 1574

EP - 1580

JO - Experimental Physiology

JF - Experimental Physiology

IS - 12

ER -