Isoform-specific and exercise intensity-dependent activation of 5'-AMP-activated protein kinase in human skeletal muscle.
1. 5'-AMP-activated protein kinase (AMPK) has been suggested to play a key role in the regulation of metabolism in skeletal muscle. AMPK is activated in treadmill-exercised and electrically stimulated rodent muscles. Whether AMPK is activated during exercise in humans is unknown. 2. We investigated the degree of activation and deactivation of alpha-isoforms of AMPK during and after exercise. Healthy human subjects performed bicycle exercise on two separate occasions at either a low ( approximately 50% maximum rate of O2 uptake (VO2,max) for 90 min) or a high ( approximately 75% VO2,max for 60 min) intensity. Biopsies from the vastus lateralis muscle were obtained before and immediately after exercise, and after 3 h of recovery. 3. We observed a 3- to 4-fold activation of the alpha2-AMPK isoform immediately after high intensity exercise, whereas no activation was observed after low intensity exercise. The activation of alpha2-AMPK was totally reversed 3 h after exercise. In contrast, alpha1-AMPK was not activated during either of the two exercise trials. 4. The in vitro AMP dependency of alpha2-AMPK was significantly greater than that of alpha1-AMPK ( approximately 3- vs. approximately 2-fold). 5. We conclude that in humans activation of alpha2-AMPK during exercise is dependent upon exercise intensity. The stable activation of alpha2-AMPK, presumably due to the activation of an upstream AMPK kinase, is compatible with a role for this kinase complex in the regulation of skeletal muscle metabolism during exercise, whereas the lack of stable alpha1-AMPK activation makes this kinase complex a less likely candidate.
Wojtaszewski
J F
JF
Copenhagen Muscle Research Centre, Department of Human Physiology, University of Copenhagen, Denmark. jwojtaszewski@aki.ku.dk
Nielsen
P
P
Hansen
B F
BF
Richter
E A
EA
Kiens
B
B
D055372:AMP-Activated Protein Kinases; D000328:Adult; D004789:Enzyme Activation / Q000502:physiology; D005080:Exercise Test; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology*; D005082:Physical Exertion / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
D007527:Isoenzymes; D009097:Multienzyme Complexes; D006003:Glycogen; C526181:PRKAA2 protein, human; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human