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 -