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2-AMPK in basal, training- and AICAR-induced
GLUT4, hexokinase II and mitochondrial protein expression in mouse muscle
1 Dept. of Human Physiology, Copenhagen Muscle Research Centre, Inst. of Exercise and Sport Sciences, Copenhagen, Denmark
2 Dep. of Genetic, Development and Molecular Pathology, Institute Cochin, INSERM, CNRS, Rene Descartes University, Paris, France
3 Copenhagen Muscle Research Centre, Dep. for Molecular Muscle Biology, Rigshospitalet, Copenhagen, Denmark
4 Copenhagen Muscle Research Centre, Dept. of Human Physiology, University of Copenhagen, Copenhagen, Denmark
* To whom correspondence should be addressed. E-mail: sbjorgensen{at}ifi.ku.dk.
We investigated the role of 
2-AMPK in basal, exercise training- and AICAR-induced protein expression of GLUT4, hexokinase II (HKII), mitochondrial markers and AMPK subunits. This was conducted in red (RG) and white (WG) gastrocnemius muscle from wildtype (WT) and 2-knockout (KO) mice after 28 days of activity wheel running or daily AICAR injection. Additional experiments were conducted to measure acute activation of AMPK by exercise and AICAR. At basal, mitochondrial markers were reduced by ~20% in 2-KO muscles compared with WT. In both muscle types, 2-AMPK activity was increased in response to both stimuli whereas 1-AMPK activity was increased only in response to exercise. Furthermore, AMPK signaling was estimated to be 60-70% lower in 2-KO compared with WT muscles. In WG, AICAR treatment increased HKII, GLUT4, Cyt. C, COX1 and CS and the 2-knockout abolished the AICAR-induced increases whereas no AICAR responses were observed in RG. Exercise-training increased GLUT4, HKII, COX1, CS and HAD protein in WG but the 2-knockout did not affect training-induced increases. Furthermore, 1-, 2-, 
1-, 2-, 
3-AMPK subunits were reduced in RG, but not in WG, by 30-60% in response to exercise training. In conclusion, the 2-knockout was associated with a ~20% reduction in mitochondrial markers in both muscle types and abolished AICAR-induced increases in protein expression in WG. However, the 2-knockout did not reduce training-induced increases in HKII, GLUT4, COX1, HAD or CS protein in WG suggesting that 2-AMPK may not be essential for metabolic adaptations of skeletal muscles to exercise-training.
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