小檗碱代谢物通过缓解氧化应激和线粒体功能障碍刺激 GLP-1 分泌

The American journal of Chinese medicine Pub Date : 2024-01-01 Epub Date: 2024-02-08 DOI:10.1142/S0192415X24500113
Wei-Li Yang, Chen-Yang Zhang, Wen-Yi Ji, Li-Li Zhao, Fang-Yuan Yang, Lin Zhang, Xi Cao
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引用次数: 0

摘要

小檗碱(BBR)是黄连的一种主要成分,具有治疗 2 型糖尿病(T2DM)和肥胖症等疾病的潜力。尽管 BBR 在血浆中的含量微乎其微,但人们相信它的代谢物在其生物活性中发挥着关键作用。虽然 BBR 被认为能促进肠 L 细胞产生 GLP-1,但其代谢物对这些细胞的细胞保护作用还有待探索。本研究探讨了 BBR 代谢物对 GLP-1 分泌的影响及其内在机制。结果发现,在六种 BBR 代谢物中,小檗碱(BBB)和巴马汀(PMT)能显著增加 GLUTag 细胞中 GLP-1 的产生和葡萄糖刺激的分泌。值得注意的是,小檗碱和巴马汀都能促进 GLP-1 和胰岛素的分泌,增强标准小鼠的葡萄糖耐量。此外,单剂量 PMT 可显著增加血浆 GLP-1,并改善高脂饮食诱导的肥胖小鼠的葡萄糖耐量。在棕榈酸或 TNF[配方:见正文]处理的 GLUTag 细胞中,BBB 和 PMT 可缓解细胞死亡、氧化应激和线粒体功能障碍。此外,它们还能有效逆转炎症诱导的 Akt 信号通路抑制。总之,这些研究结果表明,口服BBR对GLP-1分泌的有益作用主要归功于BBB和PMT的药理活性,它们对L细胞具有上述细胞保护作用,这为刺激GLP-1分泌和治疗T2DM提供了重要思路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Berberine Metabolites Stimulate GLP-1 Secretion by Alleviating Oxidative Stress and Mitochondrial Dysfunction.

Berberine (BBR) is a principal component of Rhizoma coptidis known for its therapeutic potential in treating diseases such as type 2 diabetes mellitus (T2DM) and obesity. Despite the trace levels of BBR in plasma, it's believed that its metabolites play a pivotal role in its biological activities. While BBR is recognized to promote GLP-1 production in intestinal L cells, the cytoprotective effects of its metabolites on these cells are yet to be explored. The present study investigates the effects of BBR metabolites on GLP-1 secretion and the underlying mechanisms. Our results revealed that, out of six BBR metabolites, berberrubine (BBB) and palmatine (PMT) significantly increased the production and glucose-stimulated secretion of GLP-1 in GLUTag cells. Notably, both BBB and PMT could facilitate GLP-1 and insulin secretion and enhance glucose tolerance in standard mice. Moreover, a single dose of PMT could markedly increase plasma GLP-1 and improve glucose tolerance in mice with obesity induced by a high-fat diet. In palmitic acid or TNF[Formula: see text]-treated GLUTag cells, BBB and PMT alleviated cell death, oxidative stress, and mitochondrial dysfunction. Furthermore, they could effectively reverse inflammation-induced inhibition of the Akt signaling pathway. In general, these insights suggest that the beneficial effects of orally administered BBR on GLP-1 secretion are largely attributed to the pharmacological activity of BBB and PMT by their above cytoprotective effects on L cells, which provide important ideas for stimulating GLP-1 secretion and the treatment of T2DM.

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