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长时间暴露于葡萄糖素会重新连接脂质氧化,并驱动糖尿病病的进展
Xingfeng Liu1,2,3, Jingwen Chen1,2,3, Shengying Gu1,2,3
1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
葡萄糖信号恶化糖尿病病 (DKD) 通过增加管中的脂质积累. 阻断这些细胞中的葡萄糖受体 (Gcgr) 阻止了DKD的进展,揭示了新的治疗点.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 糖尿病病 (DKD) 是导致衰竭的主要原因.
- 管道损伤是DKD进展的早期指标.
- 葡萄糖在DKD病变中的作用尚未完全理解.
研究的目的:
- 调查葡萄糖信号在糖尿病病的发展中的作用.
- 探索葡萄糖对管脂积累和损伤的影响.
- 评估在DKD中准葡萄糖信号的治疗潜力.
主要方法:
- 使用DKD小鼠模型来研究葡萄糖素注射和Gcgr敲击/敲击的效果.
- 靠近管状上皮细胞 (PTEC) 用于研究葡萄糖的长期效果.
- 分析了分子通路 (Gcgr-PKA-Creb-mTORC1) 的情况.
- 在糖尿病小鼠中评估了抗GCGR抗体治疗.
主要成果:
- 在早期的DKD中,注射葡萄糖素加剧了脂质积累和损伤.
- 在管细胞中,GCGR的淘汰/淘汰显著抑制了DKD的发展.
- 在PTEC中,长期暴露于葡萄糖诱导了"葡萄糖逆转",通过Gcgr-PKA-Creb-mTORC1通路增加了脂质生成.
- 抗GCGR抗体治疗在1型和2型糖尿病模型中有效地阻断了DKD病变的发生.
结论:
- 葡萄糖/Gcgr信号传递在PTEC脂质发生和DKD病变发生中起着至关重要的,以前未被认可的作用.
- 针对葡萄糖信号,特别是Gcgr,是DKD的有希望的治疗策略.
- 了解葡萄糖在PTEC中的双重作用 (恶化和逆转) 是DKD治疗的关键.
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