The impact of immobilisation and inflammation on the regulation of muscle mass and insulin resistance: different routes to similar end-points.
The impact of immobilisation and inflammation on the regulation of muscle mass and insulin resistance: different routes to similar end-points.
复制标题
固定化和炎症对肌肉质量和胰岛素抵抗的调节的影响：通往相似终点的不同途径。
DOI：
10.1113/jp275444
复制
发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Greenhaff PL
中科院分区：
文献类型：
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作者：
Crossland H;Skirrow S;Puthucheary ZA;Constantin-Teodosiu D;Greenhaff PL
肌肉质量损失和胰岛素敏感性是固定和炎症负担增加的常见表型特征。肌肉蛋白合成的抑制是人体固定时肌肉质量损失的主要驱动因素，包括餐后肌肉蛋白合成增加的钝化。然而，这种抑制的机制驱动因素尚未解决。固定也会引起人类肢体胰岛素抵抗，这似乎是由于肌肉收缩本身的减少。同样，缺乏机制的洞察力，我们不知道肌肉是如何感知其“不活动状态”的，也不知道肌肉胰岛素抵抗的驱动因素是否仅仅是由于不活动而产生的。在啮齿类动物和人类中，炎症状态的升高与肌肉蛋白周转和质量的重大和快速变化有关，并抑制胰岛素刺激的葡萄糖处理和氧化。有限数量的研究试图阐明在炎症负荷增加期间肌肉质量损失和胰岛素抵抗的分子调节因子，但很少同时进行。然而，有证据表明，在这种情况下，Akt（蛋白激酶B）信号传导和FOXO转录因子构成了共同信号传导途径的一部分，因此，在炎症加剧期间，萎缩和胰岛素信号传导之间的分子交叉对话被认为是可能的。综上所述，虽然肌肉质量损失和胰岛素抵抗是固定和炎症负担增加的常见终点，但由于缺乏对这些特征的机制的理解，因此对人类病理生理学的理解存在实质性差距。
Loss of muscle mass and insulin sensitivity are common phenotypic traits of immobilisation and increased inflammatory burden. The suppression of muscle protein synthesis is the primary driver of muscle mass loss in human immobilisation, and includes blunting of post‐prandial increases in muscle protein synthesis. However, the mechanistic drivers of this suppression are unresolved. Immobilisation also induces limb insulin resistance in humans, which appears to be attributable to the reduction in muscle contraction per se. Again mechanistic insight is missing such that we do not know how muscle senses its “inactivity status” or whether the proposed drivers of muscle insulin resistance are simply arising as a consequence of immobilisation. A heightened inflammatory state is associated with major and rapid changes in muscle protein turnover and mass, and dampened insulin‐stimulated glucose disposal and oxidation in both rodents and humans. A limited amount of research has attempted to elucidate molecular regulators of muscle mass loss and insulin resistance during increased inflammatory burden, but rarely concurrently. Nevertheless, there is evidence that Akt (protein kinase B) signalling and FOXO transcription factors form part of a common signalling pathway in this scenario, such that molecular cross‐talk between atrophy and insulin signalling during heightened inflammation is believed to be possible. To conclude, whilst muscle mass loss and insulin resistance are common end‐points of immobilisation and increased inflammatory burden, a lack of understanding of the mechanisms responsible for these traits exists such that a substantial gap in understanding of the pathophysiology in humans endures.