Röckl Katja S C, Hirshman Michael F, Brandauer Josef, Fujii Nobuharu, Witters Lee A, Goodyear Laurie J
Research Division, Joslin Diabetes Center and Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts 02215, USA.
Diabetes. 2007 Aug;56(8):2062-9. doi: 10.2337/db07-0255. Epub 2007 May 18.
Regular endurance exercise has profound benefits on overall health, including the prevention of obesity, cardiovascular disease, and diabetes. The objective of this study was to determine whether AMP-activated protein kinase (AMPK) mediates commonly observed adaptive responses to exercise training in skeletal muscle. Six weeks of voluntary wheel running induced a significant (P < 0.05) fiber type IIb to IIa/x shift in triceps muscle of wild-type mice. Despite similar wheel running capacities, this training-induced shift was reduced by approximately 40% in transgenic mice expressing a muscle-specific AMPKalpha2 inactive subunit. Sedentary mice carrying an AMPK-activating mutation (gamma1TG) showed a 2.6-fold increase in type IIa/x fibers but no further increase with training. To determine whether AMPK is involved in concomitant metabolic adaptations to training, we measured markers of mitochondria (citrate synthase and succinate dehydrogenase) and glucose uptake capacity (GLUT4 and hexokinase II). Mitochondrial markers increased similarly in wild-type and AMPKalpha2-inactive mice. Sedentary gamma1TG mice showed a approximately 25% increase in citrate synthase activity but no further increase with training. GLUT4 protein expression was not different in either line of transgenic mice compared with wild-type mice and tended to increase with training, although this increase was not statistically significant. Training induced a approximately 65% increase in hexokinase II protein in wild-type mice but not in AMPKalpha2-inactive mice. Hexokinase II was significantly elevated in sedentary gamma1TG mice, without an additional increase with training. AMPK is not necessary for exercise training-induced increases in mitochondrial markers, but it is essential for fiber type IIb to IIa/x transformation and increases in hexokinase II protein.
规律的耐力运动对整体健康有深远益处，包括预防肥胖、心血管疾病和糖尿病。本研究的目的是确定AMP激活的蛋白激酶（AMPK）是否介导骨骼肌中常见的运动训练适应性反应。六周的自愿轮转跑步使野生型小鼠肱三头肌中IIb型纤维向IIa/x型纤维发生显著（P<0.05）转变。尽管转基因小鼠表达肌肉特异性AMPKα2失活亚基，但在轮转跑步能力相似的情况下，这种训练诱导的转变减少了约40%。携带AMPK激活突变（γ1TG）的久坐小鼠IIa/x型纤维增加了2.6倍，但训练后未进一步增加。为了确定AMPK是否参与训练伴随的代谢适应，我们测量了线粒体标志物（柠檬酸合酶和琥珀酸脱氢酶）和葡萄糖摄取能力（GLUT4和己糖激酶II）。野生型和AMPKα2失活小鼠的线粒体标志物增加情况相似。久坐的γ1TG小鼠柠檬酸合酶活性增加了约25%，但训练后未进一步增加。与野生型小鼠相比，两种转基因小鼠品系中的GLUT4蛋白表达没有差异，且训练后有增加趋势，尽管这种增加没有统计学意义。训练使野生型小鼠己糖激酶II蛋白增加了约65%，但在AMPKα2失活小鼠中未增加。久坐的γ1TG小鼠己糖激酶II显著升高，训练后未进一步增加。AMPK对于运动训练诱导的线粒体标志物增加不是必需的，但对于IIb型纤维向IIa/x型转变和己糖激酶II蛋白增加是必不可少的。
