TFEB和TFE3通过调节胰岛素基因表达来控制葡萄糖稳态
Adrien Pasquier1, Nunzia Pastore1,2, Luca D'Orsi1
1Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
The EMBO journal
|September 15, 2023
概括
转录因子EB (TFEB) 和TFE3通过控制胰岛素的产生来调节胰腺β细胞的功能,以应对营养的可用性. 这些因素是维持葡萄糖平衡的关键.
科学领域:
- 细胞生物学 细胞生物学
- 内分泌学 在内分泌学.
- 代谢过程中的代谢.
背景情况:
- 胰腺β细胞需要精确的营养感应来产生胰岛素.
- 转录因子EB (TFEB) 和TFE3是已知的细胞代谢适应的调节者.
研究的目的:
- 研究TFEB和TFE3在不同营养条件下调节β细胞功能和胰岛素基因表达中的作用.
主要方法:
- 在营养缺乏期间研究了β细胞中的TFEB/TFE3激活和胰岛素基因表达.
- 使用了TFEB过度表达和TFEB/TFE3双淘汰模型.
- 执行了ChIP-seq以确定TFEB绑定站点.
- 分析了条件β细胞特异的Tfeb过度表达和Tfeb/Tfe3双KO小鼠.
主要成果:
- 营养缺乏激活了TFEB/TFE3,抑制了胰岛素基因表达.
- 过度表达TFEB抑制了胰岛素的转录.
- 在氨基酸剥夺期间,TFEB/TFE3的减少防止了胰岛素的抑制.
- TFEB与调节胰岛素转录的超强增强器区域结合.
- 在小鼠中对TFEB/TFE3的基因操纵严重改变了胰岛素的转录,分泌和葡萄糖耐受性.
结论:
- TFEB和TFE3是胰腺β细胞功能和胰岛素产生的关键调节者,以响应营养线索.
- 这些转录因子在营养控制的胰岛素合成和葡萄糖平衡中发挥着至关重要的作用.
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