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



  • 15′-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.
  • 2We investigated the degree of activation and deactivation of α-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 (V̇O2,max) for 90 min) or a high (∼75% V̇O2,max for 60 min) intensity. Biopsies from the vastus lateralis muscle were obtained before and immediately after exercise, and after 3 h of recovery.
  • 3We observed a 3- to 4-fold activation of the α2-AMPK isoform immediately after high intensity exercise, whereas no activation was observed after low intensity exercise. The activation of α2-AMPK was totally reversed 3 h after exercise. In contrast, α1-AMPK was not activated during either of the two exercise trials.
  • 4The in vitro AMP dependency of α2-AMPK was significantly greater than that of α1-AMPK (∼3- vs.∼2-fold).
  • 5We conclude that in humans activation of α2-AMPK during exercise is dependent upon exercise intensity. The stable activation of α2-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 α1-AMPK activation makes this kinase complex a less likely candidate.