Genetic impairment of AMPKα2 signaling does not reduce muscle glucose uptake during treadmill exercise in mice

Maarbjerg SJ, Jorgensen SB, Rose AJ, Jeppesen J, Jensen TE, Treebak JT, Birk JB, Schjerling P, Wojtaszewski JF, Richter EA. Genetic impairment of AMPK alpha 2 signaling does not reduce muscle glucose uptake during treadmill exercise in mice. Am J Physiol Endocrinol Metab 297: E924-E934, 2009. First published August 4, 2009; doi:10.1152/ajpendo.90653.2008.-Some studies suggest that the 5'-AMP-activated protein kinase ( AMPK) is important in regulating muscle glucose uptake in response to intense electrically stimulated contractions. However, it is unknown whether AMPK regulates muscle glucose uptake during in vivo exercise. We studied this in male and female mice overexpressing kinase-dead AMPK alpha 2 (AMPK-KD) in skeletal and heart muscles. Wild-type and AMPK-KD mice were exercised at the same absolute intensity and the same relative intensity (30 and 70% of individual maximal running speed) to correct for reduced exercise capacity of the AMPK-KD mouse. Muscle glucose clearance was measured using 2-deoxy-[H-3] glucose as tracer. In wild-type mice, glucose clearance was increased at 30 and 70% of maximal running speed by 40 and 350% in the quadriceps muscle and by 120 and 380% in gastrocnemius muscle, respectively. Glucose clearance was not lower in AMPK-KD muscles compared with wild-type regardless of whether animals were exercised at the same relative or the same absolute intensity. In agreement, surface membrane content of the glucose transporter GLUT4 was increased similarly in AMPK-KD and wild-type muscle in response to running. We also measured signaling of alternative exercise-sensitive pathways that might be compensatorily increased in AMPK-KD muscles. However, increases in phosphorylation of CaMKII, Trisk95, p38 MAPK, and ERK1/2 were not higher in AMPK-KD than in WT muscle. Collectively, these findings suggest that AMPK alpha 2 signaling is not essential in regulating glucose uptake in mouse skeletal muscle during treadmill exercise and that other mechanisms play a central role.