Genetic impairment of AMPKalpha2 signaling does not reduce muscle glucose uptake during treadmill exercise in mice.
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 AMPKalpha2 (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-[(3)H]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 AMPKalpha2 signaling is not essential in regulating glucose uptake in mouse skeletal muscle during treadmill exercise and that other mechanisms play a central role.
Maarbjerg
Stine J
SJ
Department of Exercise and Sport Sciences, Copenhagen Muscle Research Centre, University of Copenhagen, Copenhagen, Denmark.
Jørgensen
Sebastian B
SB
Rose
Adam J
AJ
Jeppesen
Jacob
J
Jensen
Thomas E
TE
Treebak
Jonas T
JT
Birk
Jesper B
JB
Schjerling
Peter
P
Wojtaszewski
Jørgen F P
JF
Richter
Erik A
EA
D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000502:physiology; D002404:Catheterization; D005260:Female; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000096:biosynthesis; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D010766:Phosphorylation; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012265:Ribonucleotides / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology
D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D009124:Muscle Proteins; D012265:Ribonucleotides; C495693:Slc2a4 protein, mouse; D010725:Phosphocreatine; D000620:Aminoimidazole Carboxamide; D006003:Glycogen; C548179:Prkaa1 protein, mouse; C534978:Prkaa2 protein, mouse; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D005947:Glucose