Isoform-specific and exercise intensity-dependent activation of 5'-AMP-activated protein kinase in human skeletal muscle

J Physiol. 2000 Oct 1;528 Pt 1(Pt 1):221-6. doi: 10.1111/j.1469-7793.2000.t01-1-00221.x.


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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases
  • Adult
  • Enzyme Activation / physiology
  • Exercise Test
  • Glycogen / metabolism
  • Humans
  • Isoenzymes / metabolism
  • Male
  • Multienzyme Complexes / metabolism*
  • Muscle, Skeletal / enzymology*
  • Physical Exertion / physiology*
  • Protein-Serine-Threonine Kinases / metabolism*


  • Isoenzymes
  • Multienzyme Complexes
  • Glycogen
  • PRKAA1 protein, human
  • PRKAA2 protein, human
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases