Exercise and skeletal muscle glucose transporter 4 expression: Molecular mechanisms
Exercise and skeletal muscle glucose transporter 4 expression: Molecular mechanisms
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DOI：
10.1111/j.1440-1681.2006.04362.x
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发表时间：
2006-04-01
影响因子：
2.9
通讯作者：
Hargreaves, M
中科院分区：
文献类型：
--
作者：
McGee, SL;Hargreaves, M
1. 骨骼肌是一种高度可塑性的组织，具有卓越的适应外部需求（例如运动）的能力。许多这些适应可以通过骨骼肌基因表达的变化来解释。一次运动就足以诱导一些代谢基因的表达。我们的研究重点是人类骨骼肌中葡萄糖转运蛋白亚型4（GLUT-4）表达的调控。2．单次运动后，葡萄糖转运蛋白同工型 4 基因表达立即增加，这种反应需要 GLUT-4 增强因子 (GEF) 和肌细胞增强因子 2 (MEF2) 转录因子。运动后葡萄糖转运蛋白异构体增强因子和MEF2 DNA结合活性增加，并研究了运动中MEF2在人体骨骼肌运动中调节的分子机制。 3．这些研究发现组蛋白脱乙酰酶 5 (HDAC5)、单磷酸腺苷激活蛋白激酶 (AMPK)、过氧化物酶体增殖物激活受体 γ 共激活剂 1 α (PGC-1 α) 和 p38 丝裂原激活蛋白激酶 (MAPK) 通过一系列可能涉及 MEF2 抑制、共激活和磷酸化的复杂相互作用来调节 MEF2。4。鉴于 MEF2 是许多运动反应基因所需的转录因子，这些机制可能负责调节运动期间多种代谢基因的表达。这些机制还可以为代谢疾病状态的治疗和管理提供目标，例如肥胖和2型糖尿病，其特征是骨骼肌中的线粒体功能障碍和胰岛素抵抗。
1. Skeletal muscle is a highly plastic tissue that has a remarkable ability to adapt to external demands, such as exercise. Many of these adaptations can be explained by changes in skeletal muscle gene expression. A single bout of exercise is sufficient to induce the expression of some metabolic genes. We have focused our attention on the regulation of glucose transporter isoform 4 (GLUT-4) expression in human skeletal muscle.2. Glucose transporter isoform 4 gene expression is increased immediately following a single bout of exercise, and the GLUT-4 enhancer factor (GEF) and myocyte enhancer factor 2 (MEF2) transcription factors are required for this response. Glucose transporter isoform enhancer factor and MEF2 DNA binding activities are increased following exercise, and the molecular mechanisms regulating MEF2 in exercising human skeletal muscle have also been examined.3. These studies find possible roles for histone deacetylase 5 (HDAC5), adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha) and p38 mitogen-activated protein kinase (MAPK) in regulating MEF2 through a series of complex interactions potentially involving MEF2 repression, coactivation and phosphorylation.4. Given that MEF2 is a transcription factor required for many exercise responsive genes, it is possible that these mechanisms are responsible for regulating the expression of a variety of metabolic genes during exercise. These mechanisms could also provide targets for the treatment and management of metabolic disease states, such as obesity and type 2 diabetes, which are characterized by mitochondrial dysfunction and insulin resistance in skeletal muscle.