在2型糖尿病中,TERT/FOXO1信号传递通过调节ATG9A介导的自促使小岛β细胞功能障碍
Xiao-Tian Lei1, Xiang-Fen Chen2, Sheng Qiu1
1Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 402360, China.
World journal of diabetes
|June 9, 2025
概括
端粒酶逆转录酶 (TERT) 和分叉盒O1 (FOXO1) 通过抑制ATG9A表达来抑制自,导致2型糖尿病 (T2DM) 中的小岛β细胞功能障碍. 这一途径为T2DM提供了潜在的治疗点.
科学领域:
- 分子生物学分子生物学
- 内分泌学 在内分泌学.
- 细胞生物学 细胞生物学
背景情况:
- 2型糖尿病 (T2DM) 是一个重大的全球健康挑战,需要新的治疗策略,超越目前的治疗方法,如GLP-1受体激活剂和SGLT2抑制剂.
- 有效管理T2DM需要改善血糖控制和减少慢性并发症.
研究的目的:
- 研究TERT/FOXO1在高葡萄糖诱导的小岛贝塔细胞功能障碍中的作用.
- 在这个过程中阐明涉及ATG9A介导自的机制.
主要方法:
- 在小鼠 (HFD/STZ) 和MIN6细胞 (HG处理) 中建立T2DM模型.
- 评估血糖,胰岛素水平,小岛形态,细胞增殖和细胞亡.
- 分析TERT,FOXO1,ATG9A和自蛋白表达 (LC3B,p62) 通过西式涂抹.
- 使用双化酶报告者和ChIP测试对FOXO1-ATG9A相互作用的研究.
主要成果:
- 在T2DM模型中,TERT和FOXO1的含量增加,ATG9A的表达减少.
- 小鼠的体重下降,岛屿形态受损,FBG高,胰岛素低.
- 用HG处理的细胞显示活力降低,LC3B降低,p62增加和亡率更高.
- 通过激活自细胞,FOXO1的敲击保护了岛屿β细胞功能障碍.
- TERT通过FOXO1-介导的转录激活抑制ATG9A,从而损害了自.
结论:
- TERT/FOXO1信号通路抑制ATG9A的表达,从而降低T2DM岛屿β细胞的功能.
- 这种机制突显出一种新的途径,有助于T2DM病原体的产生.
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