肌肉特异性的AXIN1和AXIN2双淘汰不会改变AMPK/mTORC1信号或葡萄糖代谢
Kaspar W Persson1, Roberto Meneses-Valdés1, Nicoline R Andersen1
1August Krogh Section for Human and Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
AXIN1和AXIN2蛋白似乎对调节骨肌肉代谢没有必要. 缺少AXIN1和AXIN2的肌肉特异性淘汰赛小鼠显示出正常的葡萄糖吸收和信号通路,挑战了先前的假设.
科学领域:
- 骨肌肉生理学 骨肌肉生理学
- 分子信号传输的方法
- 代谢调节 代谢调节 代谢调节
背景情况:
- AMP激活蛋白激酶 (AMPK) 和mTORC1是骨肌肉催化和合成的关键调节者.
- 此前曾提出AXIN1可以控制这些通路之间的切换,并促进GLUT4转位.
- 肌肉特定的AXIN1淘汰赛小鼠没有表型,这表明AXIN2可能会补偿.
研究的目的:
- 为了研究AXIN1和AXIN2在骨肌肉代谢中的作用.
- 为了确定AXIN蛋白是否对AMPK和mTORC1信号传递至关重要.
- 为了评估AXIN1/2损失对葡萄糖吸收对各种刺激的反应的影响.
主要方法:
- 产生特莫西芬诱导肌肉特异性AXIN1和AXIN2双淘汰赛 (dKO) 小鼠.
- 对dKO小鼠进行表型鉴定,以评估生理反应.
- 对AMPK和mTORC1信号通路的测量.
- 通过GLUT4转位对胰岛素,AICAR和肌肉收缩的反应来评估葡萄糖吸收.
主要成果:
- 在AXIN1/2 dKO小鼠中,AMPK和mTORC1信号传递正常.
- 作为对AICAR,胰岛素和肌肉收缩的反应,dKO小鼠的葡萄糖吸收不受影响.
- 这些发现表明,AXIN蛋白在这些代谢过程中没有重要的作用.
结论:
- 在骨肌中调节AMPK和mTORC1信号传递时,AXIN蛋白并不必不可少.
- 以前建议的AXIN1在运动刺激的AMPK激活和GLUT4葡萄糖吸收中的作用受到质疑.
- 骨肌肉的新陈代谢和葡萄糖吸收是独立于AXIN1和AXIN2.2的调节.
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