Wojtaszewski Jørgen F P, Birk Jesper B, Frøsig Christian, Holten Mads, Pilegaard Henriette, Dela Flemming
The Institute of Exercise and Sport Sciences, The Copenhagen Muscle Research Centre, University of Copenhagen, 13 Universitetsparken, 2100-Copenhagen, Denmark.
J Physiol. 2005 Apr 15;564(Pt 2):563-73. doi: 10.1113/jphysiol.2005.082669. Epub 2005 Feb 17.
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 (alpha1 and alpha2) and regulatory (beta1, beta2, gamma1, gamma2a, gamma2b and gamma3) AMPK isoforms were independent of T2DM, whereas the protein content of alpha1 (+16%), beta2 (+14%) and gamma1 (+29%) was higher and the gamma3 content was lower (-48%) in trained compared with untrained muscle (all P < 0.01). The majority of alpha protein co-immunoprecipitated with beta2 and alpha2/beta2 accounted for the majority of these complexes. gamma3 was only associated with alpha2 and beta2 subunits, and accounted for approximately 20% of all alpha2/beta2 complexes. The remaining alpha2/beta2 and the alpha1/beta2 complexes were associated with gamma1. The trimer composition was unaffected by T2DM, whereas training induced a shift from gamma3- to gamma1-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.
力量训练可增强胰岛素敏感性，是2型糖尿病（T2DM）患者耐力训练的一种替代方案。5'-腺苷酸活化蛋白激酶（AMPK）可能介导骨骼肌对运动训练的适应性反应；然而，人们对AMPK系统本身的适应性了解甚少。我们研究了力量训练和T2DM对人骨骼肌中AMPK亚型表达及异源三聚体组成的影响。10例T2DM患者和7名健康受试者对一条腿进行了6周的力量训练（T），而另一条腿保持不训练（UT）状态。在训练期前后获取肌肉活检样本。基础AMPK活性以及催化（α1和α2）和调节（β1、β2、γ1、γ2a、γ2b和γ3）AMPK亚型的蛋白质/ mRNA表达与T2DM无关，然而，与未训练的肌肉相比，训练后肌肉中α1（+ 16%）、β2（+ 14%）和γ1（+ 29%）的蛋白质含量更高，γ3含量更低（- 48%）（所有P < 0.01）。大多数α蛋白与β2共免疫沉淀，且α2 /β2构成了这些复合物的大部分。γ3仅与α2和β2亚基相关，约占所有α2 /β2复合物的20%。其余的α2 /β2和α1 /β2复合物与γ1相关。三聚体组成不受T2DM影响，而训练导致从含γ3的三聚体向含γ1的三聚体转变。这些数据对肌肉AMPK作为T2DM的主要病因提出了质疑，而T2DM患者中AMPK功能的维持使其成为一个明显的治疗靶点。在人骨骼肌中，12种可能的AMPK三聚体组合中仅存在3种，且亚基亚型的表达易受中等强度力量训练的影响，这可能会影响代谢并改善训练后肌肉中的能量稳态。
