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1 The Institute of Exercise and Sport Sciences
2 The Panum Institute
3 The August Krogh Institute, Copenhagen Muscle Research Centre, University of Copenhagen, Denmark
Strength training enhances insulin sensitivity and represents an alternative to endurance training for patients with type 2 diabetes (T2DM). The 5'AMP-activated protein kinase (AMPK) may mediate adaptations in skeletal muscle in response to exercise training; however, little is known about adaptations within the AMPK system itself. We investigated the effect of strength training and T2DM on the isoform expression and the heterotrimeric composition of the AMPK in human skeletal muscle. Ten patients with T2DM and seven healthy subjects strength trained (T) one leg for 6 weeks, while the other leg remained untrained (UT). Muscle biopsies were obtained before and after the training period. Basal AMPK activity and protein/mRNA expression of both catalytic (
1 and 2) and regulatory (ß1, ß2, 
1, 2a, 2b and 3) AMPK isoforms were independent of T2DM, whereas the protein content of 1 (+16%), ß2 (+14%) and 1 (+29%) was higher and the 3 content was lower (–48%) in trained compared with untrained muscle (all P < 0.01). The majority of protein co-immunoprecipitated with ß2 and 2/ß2 accounted for the majority of these complexes. 3 was only associated with 2 and ß2 subunits, and accounted for 
20% of all 2/ß2 complexes. The remaining 2/ß2 and the 1/ß2 complexes were associated with 1. The trimer composition was unaffected by T2DM, whereas training induced a shift from 3- to 1-containing trimers. The data question muscular AMPK as a primary cause of T2DM whereas the maintained function in patients with T2DM makes muscular AMPK an obvious therapeutic target. In human skeletal muscle only three of 12 possible AMPK trimer combinations exist, and the expression of the subunit isoforms is susceptible to moderate strength training, which may influence metabolism and improve energy homeostasis in trained muscle.
(Received 5 January 2005;
accepted after revision 10 February 2005;
first published online 17 February 2005)
Corresponding author J. F.P. Wojtaszewski: The Institute of Exercise and Sport Sciences, The Copenhagen Muscle Research Centre, University of Copenhagen, 13 Universitetsparken, 2100-Copenhagen, Denmark. Email: jwojtaszewski{at}aki.ku.dk
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