LKB1、AMPK与骨骼肌代谢的调节
LKB1 and AMPK and the regulation of skeletal muscle metabolism.
作者信息
Koh Ho-Jin, Brandauer Josef, Goodyear Laurie J
机构信息
Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
出版信息
Curr Opin Clin Nutr Metab Care. 2008 May;11(3):227-32. doi: 10.1097/MCO.0b013e3282fb7b76.
PURPOSE OF REVIEW
To address the role of LKB1 and AMP-activated protein kinase (AMPK) in glucose transport, fatty acid oxidation, and metabolic adaptations in skeletal muscle.
RECENT FINDINGS
Contraction-mediated skeletal muscle glucose transport is decreased in muscle-specific LKB1 knockout mice, but not in whole body AMPKalpha2 knockout mice or AMPKalpha2 inactive transgenic mice. Chronic activation of AMPK by 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) and beta-guanadinopropionic acid enhances mitochondrial function in skeletal muscle, but AICAR or exercise-induced increases in mitochondrial markers are preserved in skeletal muscles from whole body AMPKalpha2 or muscle-specific LKB1 knockout mice. Pharmacological activation of AMPK increases glucose transport and fatty acid oxidation in skeletal muscle. Therefore, chronic activation of AMPK may be beneficial in the treatment of obesity and type 2 diabetes.
SUMMARY
LKB1 and AMPK play important roles in regulating metabolism in resting and contracting skeletal muscle.
综述目的
探讨肝脏激酶B1（LKB1）和AMP活化蛋白激酶（AMPK）在骨骼肌葡萄糖转运、脂肪酸氧化及代谢适应中的作用。
最新发现
在肌肉特异性LKB1基因敲除小鼠中，收缩介导的骨骼肌葡萄糖转运减少，但在全身AMPKα2基因敲除小鼠或AMPKα2无活性转基因小鼠中未出现此现象。5-氨基咪唑-4-甲酰胺-1-β-D-呋喃核糖苷（AICAR）和β-胍基丙酸对AMPK的慢性激活可增强骨骼肌线粒体功能，但全身AMPKα2或肌肉特异性LKB1基因敲除小鼠骨骼肌中，AICAR或运动诱导的线粒体标志物增加得以保留。AMPK的药理学激活可增加骨骼肌葡萄糖转运和脂肪酸氧化。因此，AMPK的慢性激活可能对肥胖症和2型糖尿病的治疗有益。
总结
LKB1和AMPK在静息和收缩骨骼肌的代谢调节中发挥重要作用。
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