5′AMP activated protein kinase expression in human skeletal muscle:: effects of strength training and type 2 diabetes

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 (alpha 1 and alpha 2) and regulatory (beta 1, beta 2, gamma 1, gamma 2a, gamma 2b and gamma 3) AMPK isoforms were independent of T2DM, whereas the protein content of alpha 1 (+16%), beta 2 (+14%) and gamma 1 (+29%) was higher and the gamma 3 content was lower (-48%) in trained compared with untrained muscle (all P < 0.01). The majority of a protein co-immunoprecipitated with beta 2 and alpha 2/beta 2 accounted for the majority of these complexes. gamma 3 was only associated with alpha 2 and beta 2 subunits, and accounted for similar to 20% of all alpha 2/beta 2 complexes. The remaining alpha 2/beta 2 and the alpha 1/beta 2 complexes were associated with gamma 1. The trimer composition was unaffected by T2DM, whereas training induced a shift from gamma 3- to gamma 1-containing trimers. The data question muscular AMPK as a primary cause of T2DM whereas the maintained function inpatients 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.