- Authors:
-
-
Sylow, Lykke
;
Close
0000-0003-0905-5932
PhD, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet -
Jensen, Thomas Elbenhardt
;
Close0000-0001-6139-8268
Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet - Kleinert, Maximilian ;
- Mouatt, Joshua Roger ;
- Maarbjerg, Stine Just ;
- Jeppesen, Jacob Fuglsbjerg ;
- Prats Gavalda, Clara ;
- Chiu, Tim T ;
- Boguslavsky, Shlomit ;
- Klip, Amira ;
- Schjerling, Peter ;
-
Richter, Erik
Close0000-0002-6850-3056
Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet
-
Sylow, Lykke
;
- 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
Checking for on-site access...
