兰 (Ramulus Mori) 类化合物通过肠道微生物和岛内二甲基醇生物合成改善胰腺β细胞功能
Nan Wu1, Lusi Lu1, Yiming Liu1
1Department of Endocrinology and Metabolism, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
Biomedicines
|August 28, 2025
概括
通过调节肠道细菌以增加二甲基醇 (2-ME),改善2型糖尿病. 这种代谢物通过抑制HIF-1α信号来增强胰岛素分泌并恢复β细胞功能.
科学领域:
- 微生物学
- 代谢学
- 内分泌学
- 药理学
背景情况:
- 拉穆卢斯·莫里 (Sangzhi) 类化合物 (SZ- A) 是天然化合物,具有已知的低血糖特性,可增强胰岛素分泌.
- 人们越来越认识到肠道微生物在调节胰腺β细胞功能中的作用.
- 研究SZ-A,肠道微生物群和β细胞功能之间的相互作用对于了解糖尿病治疗至关重要.
研究的目的:
- 通过调节肠道微生物群及其代谢物来确定桑奇类 (SZ-A) 是否能改善β细胞功能.
- 在2型糖尿病模型中阐明SZ-A低血糖作用的机制.
主要方法:
- 使用高脂肪饮食和链杆菌素建立了2型糖尿病 (T2DM) 的小鼠模型.
- 随后进行16S rRNA测序以分析肠道微生物群和液体染色体质谱以分析代谢物.
- 使用单细胞RNA测序 (scRNA-seq) 来分析胰腺β细胞中的基因表达和信号通路.
主要成果:
- 在T2DM小鼠中,SZ- A治疗显著缓解了高血糖和小岛细胞数量的增加.
- SZ-A调节了肠道微生物组成,增加了像乳酸菌这样的有益细菌,并增加了代谢物2-甲基醇 (2-ME) 的水平.
- scRNA- seq显示小岛中COMT+细胞增加,这表明局部2- ME合成,而体外研究显示2- ME抑制了HIF- 1α信号传递并促进了胰岛素分泌.
结论:
- 桑吉类药物 (SZ-A) 改善胰腺β细胞功能,恢复2型糖尿病的平衡.
- 通过调节肠道微生物群和直接产生岛屿,SZ-A通过增强2-甲氧二醇 (2-ME) 水平来实现这些效应.
- 该机制涉及2-ME抑制HIF-1α信号,突出显示了糖尿病的新疗法.
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