Human Skeletal Muscle Disuse Atrophy: Effects on Muscle Protein Synthesis, Breakdown, and Insulin Resistance-A Qualitative Review.
Human Skeletal Muscle Disuse Atrophy: Effects on Muscle Protein Synthesis, Breakdown, and Insulin Resistance-A Qualitative Review.
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DOI：
10.3389/fphys.2016.00361
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发表时间：
2016
影响因子：
4
通讯作者：
Atherton PJ
中科院分区：
文献类型：
--
作者：
Rudrappa SS;Wilkinson DJ;Greenhaff PL;Smith K;Idris I;Atherton PJ
人口老龄化和代谢综合征全球大流行带来的日益沉重的负担要求进一步了解可改变的风险因素，以减少与这些疾病相关的残疾和发病率。废用性骨骼肌萎缩（有时称为“简单”萎缩）和胰岛素抵抗是由久坐行为和强制固定期引起的“非病理性”事件，因为骨折或择期矫形手术。然而，调节废用性萎缩和胰岛素抵抗的过程和驱动因素以及相关的分子事件仍然不清楚，特别是在人类中。本综述的目的是目前的知识之间的关系肌肉蛋白质周转，胰岛素抵抗和肌肉萎缩在废用，主要是在人类。固定降低禁食状态肌肉蛋白质合成（MPS），并诱导进食状态的“合成代谢抵抗”。虽然缺乏肌肉蛋白分解（MPB）的动态测量排除了定义MPB在废用性萎缩中的明确作用，但一些蛋白水解“标志物”研究（例如，MPB基因）提示潜在的早期升高。制动也诱导肌肉胰岛素抵抗（IR）。此外，肌肉萎缩的轨迹似乎在持续IR状态下加速（例如，II型糖尿病），表明IR可能有助于在这些条件下的肌肉废用性萎缩。尽管如此，不同肌肉群之间胰岛素敏感性差异的作用及其对萎缩率的影响仍不清楚。多方面的时间过程研究胰岛素抵抗和肌肉蛋白质周转的集体作用，在人类废用性肌肉萎缩的设置，需要促进适当的对策和有效的康复方案的发展。
The ever increasing burden of an aging population and pandemic of metabolic syndrome worldwide demands further understanding of the modifiable risk factors in reducing disability and morbidity associated with these conditions. Disuse skeletal muscle atrophy (sometimes referred to as “simple” atrophy) and insulin resistance are “non-pathological” events resulting from sedentary behavior and periods of enforced immobilization e.g., due to fractures or elective orthopedic surgery. Yet, the processes and drivers regulating disuse atrophy and insulin resistance and the associated molecular events remain unclear—especially in humans. The aim of this review is to present current knowledge of relationships between muscle protein turnover, insulin resistance and muscle atrophy during disuse, principally in humans. Immobilization lowers fasted state muscle protein synthesis (MPS) and induces fed-state “anabolic resistance.” While a lack of dynamic measurements of muscle protein breakdown (MPB) precludes defining a definitive role for MPB in disuse atrophy, some proteolytic “marker” studies (e.g., MPB genes) suggest a potential early elevation. Immobilization also induces muscle insulin resistance (IR). Moreover, the trajectory of muscle atrophy appears to be accelerated in persistent IR states (e.g., Type II diabetes), suggesting IR may contribute to muscle disuse atrophy under these conditions. Nonetheless, the role of differences in insulin sensitivity across distinct muscle groups and its effects on rates of atrophy remains unclear. Multifaceted time-course studies into the collective role of insulin resistance and muscle protein turnover in the setting of disuse muscle atrophy, in humans, are needed to facilitate the development of appropriate countermeasures and efficacious rehabilitation protocols.