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

Lykke Sylow; Thomas Elbenhardt Jensen; Maximilian Kleinert; Joshua Roger Mouatt; Stine Just Maarbjerg; Jacob Fuglsbjerg Jeppesen; Clara Prats Gavalda; Tim T Chiu; Shlomit Boguslavsky; Amira Klip; Peter Schjerling; Erik Richter

doi:10.2337/db12-0491

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

Authors:

Sylow, Lykke ;
Close
0000-0003-0905-5932
PhD, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet
Jensen, Thomas Elbenhardt ;
Close
0000-0001-6139-8268
Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet
Kleinert, Maximilian ;
Close
PhD, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet
Mouatt, Joshua Roger ;
Close
PhD, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet
Maarbjerg, Stine Just ;
Close
Diabetes Research Unit, Novo Nordisk A/S
Jeppesen, Jacob Fuglsbjerg ;
Close
Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet
Prats Gavalda, Clara ;
Close
Section of Systems Biology Research, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet
Chiu, Tim T ;
Close
Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario
Boguslavsky, Shlomit ;
Close
Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario
Klip, Amira ;
Close
Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario
Schjerling, Peter ;
Close
Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
Richter, Erik
Close
0000-0002-6850-3056
Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet

DOI:

10.2337/db12-0491

Abstract:

In skeletal muscle, the actin cytoskeleton-regulating GTPase, Rac1, is necessary for insulin-dependent GLUT4 translocation. Muscle contraction increases glucose transport and represents an alternative signaling pathway to insulin. Whether Rac1 is activated by muscle contraction and regulates contraction-induced glucose uptake is unknown. Therefore, we studied the effects of in vivo exercise and ex vivo muscle contractions on Rac1 signaling and its regulatory role in glucose uptake in mice and humans. Muscle Rac1-GTP binding was increased after exercise in mice (~60-100%) and humans (~40%), and this activation was AMP-activated protein kinase independent. Rac1 inhibition reduced contraction-stimulated glucose uptake in mouse muscle by 55% in soleus and by 20-58% in extensor digitorum longus (EDL; P <0.01). In agreement, the contraction-stimulated increment in glucose uptake was decreased by 27% (P = 0.1) and 40% (P <0.05) in soleus and EDL muscles, respectively, of muscle specific inducible Rac1 knockout mice. Furthermore, depolymerization of the actin cytoskeleton decreased contraction-stimulated glucose uptake by 100% and 62% (P <0.01) in soleus and EDL muscles, respectively. These are the first data to show that Rac1 is activated during muscle contraction in murine and human skeletal muscle and suggest that Rac1 and possibly the actin cytoskeleton are novel regulators of contraction-stimulated glucose uptake.

Type:

Journal article

Language:

English

Published in:

Diabetes, 2013, Vol 62, Issue 4, p. 1139-1151

Main Research Area:

Science/technology

Publication Status:

Published

Review type:

Peer Review

Submission year:

2013

Scientific Level:

Scientific

ID:

239957987

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

Full text access

On-site access

At institution

Metrics

Example	Finds records
water{}	containing the word "water".
water supplies"{}"	containing the phrase "water supplies".
author:"Doe, John"author:"{}"	containing the prase "Doe, John" in the author field.
title:IEEEtitle:{}	containing the word "IEEE" in the title field.
Need more help?	Advanced search tutorial