Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, P. R. China.
Am J Chin Med. 2024;52(1):253-274. doi: 10.1142/S0192415X24500113. Epub 2024 Feb 8.
Berberine (BBR) is a principal component of 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.
小檗碱（BBR）是黄连的主要成分之一，以其在治疗 2 型糖尿病（T2DM）和肥胖症等疾病方面的治疗潜力而闻名。尽管 BBR 在血浆中的含量很低，但人们认为其代谢物在其生物活性中起着关键作用。虽然 BBR 被认为能促进肠道 L 细胞产生 GLP-1，但 BBR 代谢物对这些细胞的细胞保护作用尚未得到探索。本研究调查了 BBR 代谢物对 GLP-1 分泌的影响及其潜在机制。我们的研究结果表明，在 BBR 的 6 种代谢物中，小檗红碱（BBB）和巴马汀（PMT）显著增加了 GLUTag 细胞中 GLP-1 的产生和葡萄糖刺激分泌。值得注意的是，BBB 和 PMT 均可促进 GLP-1 和胰岛素的分泌，并改善标准小鼠的葡萄糖耐量。此外，单次给予 PMT 可显著增加肥胖小鼠的血浆 GLP-1 水平并改善其葡萄糖耐量，肥胖由高脂肪饮食诱导。在棕榈酸或 TNF[Formula: see text]处理的 GLUTag 细胞中，BBB 和 PMT 减轻了细胞死亡、氧化应激和线粒体功能障碍。此外，它们可以有效逆转炎症诱导的 Akt 信号通路抑制。总的来说，这些发现表明，口服 BBR 对 GLP-1 分泌的有益作用主要归因于 BBB 和 PMT 的药理活性，它们通过对 L 细胞的上述细胞保护作用，为刺激 GLP-1 分泌和治疗 T2DM 提供了重要思路。
