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J Physiol Volume 528, Number 1, 221-226, October 1, 2000
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The Journal of Physiology (2000), 528.1, pp. 221-226
© Copyright 2000 The Physiological Society

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

Jørgen F. P. Wojtaszewski, Pernille Nielsen, Bo F. Hansen*, Erik A. Richter and Bente Kiens

Copenhagen Muscle Research Centre, Department of Human Physiology, University of Copenhagen and *Diabetes Biology, Novo Nordisk, Bagsvaerd, Denmark

  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 (~50% maximum rate of O2 uptake (VO2,max) for 90 min) or a high (~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 (~3- vs. ~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.




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