Genetic impairment of AMPK{alpha}2 signaling does not reduce muscle glucose uptake during treadmill exercise in mice

TY - JOUR

T1 - Genetic impairment of AMPK{alpha}2 signaling does not reduce muscle glucose uptake during treadmill exercise in mice

AU - Maarbjerg, Stine Just

AU - Jørgensen, Sebastian Beck

AU - Rose, Adam John

AU - Jeppesen, Jacob

AU - Jensen, Thomas Elbenhardt

AU - Treebak, Jonas Thue

AU - Birk, Jesper Bratz

AU - Schjerling, Peter

AU - Wojtaszewski, Jørgen

AU - Richter, Erik

N1 - CURIS 2009 5200 103

PY - 2009

Y1 - 2009

N2 - 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 if AMPK regulates muscle glucose uptake during in vivo exercise. We studied this in male and female mice over-expressing kinase-dead alpha2-AMPK (AMPK-KD) in skeletal and heart muscles. Wildtype 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 [3H]-2-deoxy-glucose as tracer. In wildtype 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 to wildtype 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 wildtype muscle in response to running. We also measured signaling of alternative exercise sensitive pathways which 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 alpha2-AMPK signaling is not essential in regulating glucose uptake in mouse skeletal muscle during treadmill exercise and that other unknown mechanisms play a central role. Key words: exercise, glucose uptake, AMPK.

AB - 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 if AMPK regulates muscle glucose uptake during in vivo exercise. We studied this in male and female mice over-expressing kinase-dead alpha2-AMPK (AMPK-KD) in skeletal and heart muscles. Wildtype 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 [3H]-2-deoxy-glucose as tracer. In wildtype 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 to wildtype 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 wildtype muscle in response to running. We also measured signaling of alternative exercise sensitive pathways which 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 alpha2-AMPK signaling is not essential in regulating glucose uptake in mouse skeletal muscle during treadmill exercise and that other unknown mechanisms play a central role. Key words: exercise, glucose uptake, AMPK.

U2 - 10.1152/ajpendo.90653.2008

DO - 10.1152/ajpendo.90653.2008

M3 - Journal article

C2 - 19654283

SN - 0193-1849

VL - 297

SP - E924-E934

JO - American Journal of Physiology: Endocrinology and Metabolism

JF - American Journal of Physiology: Endocrinology and Metabolism

IS - 4

ER -