TRPM7激酶调节小鼠α细胞增殖和葡萄糖生成
Severin Boulassel1, Pascale C F Schreier1, Andreas Beck2
1Walther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, LMU Munich, Munich, Germany.
TRPM7激酶/mTOR通路对于小鼠α细胞功能至关重要. 失去TRPM7激酶会损害mTOR信号传递,减少α细胞的增殖和葡萄糖分泌.
科学领域:
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 葡萄糖稳定对于葡萄糖稳定至关重要,但阿尔法细胞调节尚未完全理解.
- 暂时受体潜在的梅拉斯7 (TRPM7) 离子通道具有激酶域并影响mTOR信号传递.
- 哺乳动物的拉巴amycin目标 (mTOR) 途径是对α细胞调节的核心.
研究的目的:
- 研究TRPM7在α细胞生物学中的作用.
- 确定TRPM7是否与α细胞中的mTOR信号通路相互作用.
主要方法:
- 从野生型 (WT) 和TRPM7激酶不活跃 (Trpm7R/R) 鼠标中分离出来的小岛.
- 使用了Bio-Plex,RNA测序,ELISA,qRT-PCR,西式涂抹,免疫细胞化学和补丁.
- 使用的αTC1c9细胞和TRPM7抑制剂NS8593.
主要成果:
- 在Trpm7R/R小岛上,mTOR信号受损,葡萄糖分减少.
- 由于下调的Gcg和Mafb,葡萄糖含量下降.
- Trpm7R/R阿尔法细胞显示减少了增殖和增加了亡.
- 抑制TRPM7抑制了mTOR信号传递,阿尔法细胞的识别和增殖.
结论:
- TRPM7激酶活性对于维持α细胞功能至关重要.
- 在小鼠中,TRPM7激酶/mTOR信号轴关键调节α细胞增殖和葡萄糖分泌.
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