暴露于会通过抑制肝脏糖原合成和增强葡萄糖生成来增加禁食血葡萄糖
Yue Wang1, Lei Zhang2, Miao He3
1Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China; School of Public Health, Shenyang Medical College, No. 146 Huanghe North Street, Shenyang 110034, China.
Journal of hazardous materials
|October 17, 2025
概括
暴露与更高的空腹血葡萄糖 (FPG) 水平有关. 这项研究揭示了通过抑制PI3K/Akt路径来破坏肝脏葡萄糖代谢,增加糖尿病风险.
科学领域:
- 环境健康 环境健康
- 代谢障碍 代谢障碍 代谢障碍
- 毒理学 毒理学 毒理学
背景情况:
- (Co) 是一个无处不在的环境过渡金属.
- 同期暴露与糖尿病风险增加和快速血葡萄糖 (FPG) 的升高有关.
- 共同诱导的FPG升高背后的确切机制尚不清楚.
研究的目的:
- 在人类群体中调查尿液中Co水平和FPG之间的关系.
- 在肝细胞和小鼠中阐明同诱导葡萄糖代谢功能障碍的分子机制.
主要方法:
- 人口调查将尿路Co与FPG相关联.
- 代谢学和网络毒理学分析以确定关键途径.
- 在体内 (小鼠) 和体外 (MIHA肝细胞) 实验以验证机制.
主要成果:
- 在尿液中的Co度和FPG水平之间观察到正相关性.
- 暴露抑制了肝脏中的PI3K/Akt信号通路.
- Co 抑制了肝脏葡萄糖吸收和葡萄糖原合成,同时增强了葡萄糖生成.
- 通过对miR-148b-3p进行下调,对PTEN表达进行了对高调节,从而导致PI3K/Akt抑制.
结论:
- 暴露于会破坏肝脏葡萄糖代谢,导致FPG升高.
- PI3K/Akt信号通路是肝脏联合诱导的代谢干扰的关键目标.
- 这些发现突出了在代谢障碍中的作用的新机制.
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