Long Yun Chau, Zierath Juleen R
Karolinska Institutet, Dept. of Molecular Medicine and Surgery, von Eulers väg 4, S-171 77 Stockholm, Sweden.
Am J Physiol Endocrinol Metab. 2008 Sep;295(3):E545-52. doi: 10.1152/ajpendo.90259.2008. Epub 2008 Jun 10.
Skeletal muscle fibers differ considerably in their metabolic and physiological properties. Skeletal muscle displays a high degree of metabolic flexibility, which allows the myofibers to adapt to various physiological demands by shifting energy substrate utilization. Transcriptional events play a pivotal role in the metabolic adaptations of skeletal muscle. The expression of genes essential for skeletal muscle glucose and lipid metabolism is tightly coordinated in support of a shift in substrate utilization. AMP-activated protein kinase (AMPK) and calcineurin (a calcium-regulated serine/threonine protein phosphatase) regulate skeletal muscle metabolic gene expression programs in response to changes in the energy status and levels of neuronal input, respectively. AMPK and calcineurin activate transcriptional regulators such as peroxisome proliferator-activated receptor-gamma coactivator-1alpha and myocyte enhancer factor as well as increase skeletal muscle oxidative capacity and mitochondrial gene expression. Activation of either the AMPK or calcineurin pathway can also enhance the glycogen storage capacity and insulin sensitivity in skeletal muscle. Characterization of pathways governing skeletal muscle metabolism offers insight into physiological and pharmacological strategies to prevent or ameliorate peripheral insulin resistance associated with metabolic disorders such as type 2 diabetes.
骨骼肌纤维在代谢和生理特性上有很大差异。骨骼肌表现出高度的代谢灵活性，这使得肌纤维能够通过改变能量底物利用来适应各种生理需求。转录事件在骨骼肌的代谢适应中起关键作用。骨骼肌葡萄糖和脂质代谢所必需的基因表达紧密协调，以支持底物利用的转变。AMP激活的蛋白激酶（AMPK）和钙调神经磷酸酶（一种钙调节的丝氨酸/苏氨酸蛋白磷酸酶）分别响应能量状态和神经元输入水平的变化，调节骨骼肌代谢基因表达程序。AMPK和钙调神经磷酸酶激活转录调节因子，如过氧化物酶体增殖物激活受体γ共激活因子-1α和肌细胞增强因子，同时增加骨骼肌氧化能力和线粒体基因表达。激活AMPK或钙调神经磷酸酶途径也可以增强骨骼肌的糖原储存能力和胰岛素敏感性。对骨骼肌代谢调控途径的表征有助于深入了解预防或改善与2型糖尿病等代谢紊乱相关的外周胰岛素抵抗的生理和药理策略。
