复星可以通过C2C12细胞中的DDIT4/mTOR通路改善棕酸诱导的胰岛素抵抗
Xinyan Pan1, Chunqiao Liu2, Xing Wang2
1Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China.
Molecular medicine reports
|August 18, 2023
概括
复星 (RSV) 通过调节DDIT4/mTOR/IRS-1/PI3K/AKT/GLUT4通路,改善C2C12细胞中棕酸诱导的胰岛素抵抗 (IR). 这增强了葡萄糖的吸收并改善了脂质代谢,为IR提供了潜在的治疗策略.
科学领域:
- 细胞生物学 细胞生物学
- 代谢研究研究 代谢研究
- 分子生物学分子生物学
背景情况:
- 胰岛素抵抗 (IR) 是一种代谢障碍,其特征是葡萄糖吸收和脂质积累受损.
- 棕酸 (PA) 是一种和脂肪酸,已知可以在各种细胞模型中诱导IR.
- 复星 (RSV) 是一种天然的多,对代谢性疾病具有潜在的治疗益处.
研究的目的:
- 使用C2C12细胞建立PA诱导IR的细胞模型.
- 阐明RSV改善PA诱导的IR的分子机制.
- 研究DDIT4/mTOR/IRS-1/PI3K/AKT/GLUT4信号通路在RSV影响中的作用.
主要方法:
- 用PA治疗C2C12神经细胞以诱导IR,有或没有RSV.
- 干预组包括DDIT4siRNA和mTOR激动剂 (MHY1485),以探测途径的参与.
- 葡萄糖和脂质代谢的关键分子标记物和信号通路组件 (DDIT4,mTOR,IRS-1,PI3K,AKT,GLUT4) 用qPCR和西式斑点测试进行了评估.
- 油红色O染色被用于评估脂质沉积.
主要成果:
- 治疗PA降低了葡萄糖吸收,增加了脂质沉积,改变了信号通路组件酸化 (增加了p-IRS-1,p-mTOR,p-p70S6K;降低了p-PI3K,p-AKT,GLUT4,DDIT4).
- 通过调节p-PI3K,p-AKT,GLUT4和DDIT4上升,同时调节p-IRS-1,mTOR和p70S6K下降,RSV治疗逆转了这些影响,降低了脂质积累和改善了葡萄糖代谢.
- 用MHY1485击败DDIT4或激活mTOR减弱了RSV的有益作用,证实了该途径的重要性.
结论:
- Ресвератрол有效地改善了C2C12细胞中棕酸诱导的胰岛素抵抗.
- 该机制涉及对DDIT4/mTOR/IRS-1/PI3K/AKT/GLUT4信号通路的调制.
- RSV的有益作用与改善的葡萄糖和脂质代谢有关,这表明它对IR的治疗潜力.
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