Role of AMPK alpha 2 in basal, training-, and AICAR-induced GLUT4, hexokinase II, and mitochondrial protein expression in mouse muscle

Role of AMPK alpha 2 in basal, training-, and AICAR-induced GLUT4, hexokinase II, and mitochondrial protein expression in mouse muscle. Am J Physiol Endocrinol Metab 292: E331-E339, 2007. First published September 5, 2006; doi:10.1152/ajpendo.00243.2006.-We investigated the role of AMPK alpha 2 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 gastrocnemius (WG) muscle from wild-type (WT) and alpha 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 similar to 20% in alpha 2-KO muscles compared with WT. In both muscle types, AMPK alpha 2 activity was increased in response to both stimuli, whereas AMPK alpha 1 activity was increased only in response to exercise. Furthermore, AMPK signaling was estimated to be 60-70% lower in alpha 2-KO compared with WT muscles. In WG, AICAR treatment increased HKII, GLUT4, cytochrome c, COX-1, and CS, and the alpha 2-KO abolished the AICAR-induced increases, whereas no AICAR responses were observed in RG. Exercise training increased GLUT4, HKII, COX-1, CS, and HAD protein in WG, but the alpha 2-KO did not affect training- induced increases. Furthermore, AMPK alpha 1, -alpha 2, -beta 1, -beta 2, and -gamma 3 subunits were reduced in RG, but not in WG, by 30-60% in response to exercise training. In conclusion, the alpha 2-KO was associated with an similar to 20% reduction in mitochondrial markers in both muscle types and abolished AICAR-induced increases in protein expression in WG. However, the alpha 2-KO did not reduce training-induced increases in HKII, GLUT4, COX-1, HAD, or CS protein in WG, suggesting that AMPK alpha 2 may not be essential for metabolic adaptations of skeletal muscles to exercise training.