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Rac1 and AMPK Account for the Majority of Muscle Glucose Uptake Stimulated by Ex Vivo Contraction but Not In Vivo Exercise

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  • Lykke Sylow
  • Lisbeth Møller
  • Maximilian Kleinert
  • Gommaar D'Hulst
  • Estelle De Groote
  • Peter Schjerling
  • Gregory R Steinberg
  • Thomas Jensen
  • Erik Richter
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Exercise bypasses insulin resistance to increase glucose uptake in skeletal muscle and therefore represents an important alternative to stimulate glucose uptake in insulin-resistant muscle. 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.
Muscle-specific knockout (mKO) of Rac1, a kinasedead a2 AMPK (a2KD), and double knockout (KO) of b1 and b2 AMPK subunits (b1b2 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 b1b2 KO or a2KD, contraction-stimulated glucose transport was almost completely inhibited. Importantly, a2KD+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 a2KD. 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 a2 AMPK, regulates muscle glucose uptake during submaximal exercise in vivo.
Original languageEnglish
JournalDiabetes
Volume66
Pages (from-to)1548-1559
Number of pages12
ISSN0012-1797
DOIs
Publication statusPublished - Jun 2017

ID: 52759439