Frost Robert A, Lang Charles H
Department of Cellular and Molecular Physiology, The Penn State University College of Medicine, Hershey, PA 17033, USA.
J Appl Physiol (1985). 2007 Jul;103(1):378-87. doi: 10.1152/japplphysiol.00089.2007. Epub 2007 Mar 1.
Although the boundaries of skeletal muscle size are fundamentally determined by genetics, this dynamic tissue also demonstrates great plasticity in response to environmental and hormonal factors. Recent work indicates that contractile activity, nutrients, growth factors, and cytokines all contribute to determining muscle mass. Muscle responds not only to endocrine hormones but also to the autocrine production of growth factors and cytokines. Skeletal muscle synthesizes anabolic growth factors such as insulin-like growth factor (IGF)-I and potentially inhibitory cytokines such as interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and myostatin. These self-regulating inputs in turn influence muscle metabolism, including the use of nutrients such as glucose and amino acids. These changes are principally achieved by altering the activity of the protein kinase known as protein kinase B or Akt. Akt plays a central role in integrating anabolic and catabolic responses by transducing growth factor and cytokine signals via changes in the phosphorylation of its numerous substrates. Activation of Akt stimulates muscle hypertrophy and antagonizes the loss of muscle protein. Here we review the many signals that funnel through Akt to alter muscle mass.
虽然骨骼肌大小的界限从根本上由基因决定，但这种动态组织在对环境和激素因素作出反应时也表现出很大的可塑性。最近的研究表明，收缩活动、营养物质、生长因子和细胞因子都有助于决定肌肉质量。肌肉不仅对内分泌激素有反应，而且对生长因子和细胞因子的自分泌产生也有反应。骨骼肌合成诸如胰岛素样生长因子（IGF）-I等合成代谢生长因子以及诸如白细胞介素（IL）-6、肿瘤坏死因子（TNF）-α和肌肉生长抑制素等潜在抑制性细胞因子。这些自我调节的输入反过来又影响肌肉代谢，包括葡萄糖和氨基酸等营养物质的利用。这些变化主要是通过改变称为蛋白激酶B或Akt的蛋白激酶的活性来实现的。Akt通过其众多底物磷酸化的变化转导生长因子和细胞因子信号，在整合合成代谢和分解代谢反应中起核心作用。Akt的激活刺激肌肉肥大并拮抗肌肉蛋白的丢失。在这里，我们综述了许多通过Akt来改变肌肉质量的信号。
