Myostatin decreases with aerobic exercise and associates with insulin resistance.
Myostatin decreases with aerobic exercise and associates with insulin resistance.
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DOI：
10.1249/mss.0b013e3181e0b9a8
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发表时间：
2010-11
影响因子：
4.1
通讯作者：
Kraus WE
中科院分区：
文献类型：
--
作者：
Hittel DS;Axelson M;Sarna N;Shearer J;Huffman KM;Kraus WE
越来越多的证据表明，骨骼肌产生和分泌具有生物活性的蛋白质或“肌因子”，促进器官系统之间的代谢串扰。肌生长抑制素（一种抑制肌肉生长发育的合成代谢抑制剂）的表达增加与肥胖和胰岛素抵抗有关。尽管有这些有趣的发现，很少有研究将肌肉生长抑制素和胰岛素抵抗联系起来。为了更详细地探讨这种关系，我们量化了10名胰岛素抵抗的中年（53.1±5.5岁）男性在进行6个月的适度有氧运动训练（1200千卡/周，40-55%峰值VO2）前后肌肉和血浆中的肌肉生长抑制素蛋白。为了建立病例效应关系，我们还向C57/Bl6雄性小鼠注射了高生理水平的重组肌生长抑制素蛋白。有氧运动后肌肉肌肉生长抑制素蛋白水平（37%，P=0.042, n=10）和相应血浆样品（训练前28.7 ng/ml至训练后22.8 ng/ml， P=0.003, n=9）均下降。此外，血浆肌生长抑制素水平与胰岛素敏感性之间存在很强的相关性（R2 = 0.82， P<0.001, n=9），表明两者之间存在因果关系，随后在注射肌生长抑制素的小鼠中诱导胰岛素抵抗证实了这一关系。血浆肌生长抑制素水平的适度增加（44%）也与胰岛素刺激下肌肉和肝脏中AKT （Thr308）磷酸化的显著降低有关。这些发现表明，肌肉和血浆肌生长抑制素蛋白水平均受有氧运动的调节，此外，肌生长抑制素在缺乏运动的获得性胰岛素抵抗的因果途径中。
There is mounting evidence that skeletal muscle produces and secretes biologically active proteins or “myokines” that facilitate metabolic cross talk between organ systems. The increased expression of myostatin, a secreted anabolic inhibitor of muscle growth and development, has been associated with obesity and insulin resistance. Despite these intriguing findings, there have been few studies linking myostatin and insulin resistance. To explore this relationship in more detail, we quantified myostatin protein in muscle and plasma from 10 insulin-resistant, middle aged (53.1 ± 5.5 years) men before and after 6 months of moderate aerobic exercise training (1200 kcal/wk at 40–55% peak VO2). To establish a case-effect relationship we also injected C57/Bl6 male mice with high-physiologic levels of recombinant myostatin protein. Myostatin protein levels were shown to decrease in muscle (37%, P=0.042, n=10) and matching plasma samples (28.7 pre-training to 22.8 ng/ml post-training, P=0.003, n=9) with aerobic exercise. Furthermore, the strong correlation between plasma myostatin levels and insulin sensitivity (R2 = 0.82, P<0.001, n=9) suggested a cause-effect relationship that was subsequently confirmed by inducing insulin resistance in myostatin-injected mice. A modest increase (44%) in plasma myostatin levels was also associated with significant reductions in the insulin-stimulated phosphorylation of AKT (Thr308) in both muscle and liver of myostatin treated animals. These findings indicate that both muscle and plasma myostatin protein levels are regulated by aerobic exercise and furthermore, that myostatin is in the causal pathway of acquired insulin resistance with physical inactivity.