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Both Rac1 and AMPK have been shown to partly regulate contraction-stimulated muscle glucose uptake, but whether those two signaling pathways jointly account for the entire signal to glucose transport is unknown. We therefore studied the ability of contraction and exercise to stimulate glucose transport in isolated muscles with AMPK loss of function combined with either pharmacological inhibition or genetic deletion of Rac1.<\/jats:p>\n               <jats:p>Muscle-specific knockout (mKO) of Rac1, a kinase-dead \u03b12 AMPK (\u03b12KD), and double knockout (KO) of \u03b21 and \u03b22 AMPK subunits (\u03b21\u03b22 KO) each partially decreased contraction-stimulated glucose transport in mouse soleus and extensor digitorum longus (EDL) muscle. Interestingly, when pharmacological Rac1 inhibition was combined with either AMPK \u03b21\u03b22 KO or \u03b12KD, contraction-stimulated glucose transport was almost completely inhibited. Importantly, \u03b12KD+Rac1 mKO double-transgenic mice also displayed severely impaired contraction-stimulated glucose transport, whereas exercise-stimulated glucose uptake in vivo was only partially reduced by Rac1 mKO with no additive effect of \u03b12KD. It is concluded that Rac1 and AMPK together account for almost the entire ex vivo contraction response in muscle glucose transport, whereas only Rac1, but not \u03b12 AMPK, regulates muscle glucose uptake during submaximal exercise in vivo.<\/jats:p>","DOI":"10.2337\/db16-1138","type":"journal-article","created":{"date-parts":[[2017,4,8]],"date-time":"2017-04-08T00:40:19Z","timestamp":1491612019000},"page":"1548-1559","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":58,"title":["Rac1 and AMPK Account for the Majority of Muscle Glucose Uptake Stimulated by Ex Vivo Contraction but Not In Vivo Exercise"],"prefix":"10.2337","volume":"66","author":[{"given":"Lykke","family":"Sylow","sequence":"first","affiliation":[{"name":"Molecular Physiology Group, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, 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