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 (similar to 50% maximum rate of O-2 uptake ((V)over dot (O2max)) for 90 min) or a high (similar to 75% (V)over dot(O2max) 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 lon intensity exercise. The activation of alpha2-AMPK was totally reversed 3 h after exercise. In contrast, alpha1-AMPK was not activated during either of tilt: two exercise trials. 4. The in vitro AMP dependency of alpha2-AMPK was significantly greater than that of alpha1-AMPK (similar to3- vs. similar to2-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.