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

Abstract

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.

Figure 1

Effects of exercise on isoform-specific AMPK activity Muscle α2-AMPK (A) and α1-AMPK (B) activity in the low intensity exercise trial (top panels) and in the high intensity exercise trial (bottom panels). Activities were measured in vitro in the absence (○) or presence (•) of AMP. Significant differences (P < 0.05) from Basal as well as 3h Post Ex (*) and from the same measurement in the absence of AMP (†) are indicated. Data are presented as means ±s.e.m., n = 6–7.