Chikusetsu saponin IVa protects pancreatic β cell against intermittent high glucose-induced injury by activating Wnt/β-catenin/TCF7L2 pathway
Chikusetsu saponin IVa protects pancreatic β cell against intermittent high glucose-induced injury by activating Wnt/β-catenin/TCF7L2 pathway
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Chikusetsu 皂苷 IVa 通过激活 Wnt/β-catenin/TCF7L2 通路保护胰腺 β 细胞免受间歇性高糖诱导的损伤
DOI：
10.18632/aging.102702
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发表时间：
2020-01-31
期刊：
影响因子：
5.2
通讯作者：
Qiao, Boling
中科院分区：
文献类型：
--
作者：
Cui, Jia;Duan, Jialin;Qiao, Boling
血糖波动引起的胰岛β细胞质量减少在T2 DM的发生发展中起重要作用。七叶皂苷Iva(CHS)对糖尿病及相关损伤有保护作用。本研究旨在探讨CHS在β细胞损伤中的作用及其可能的机制。本研究采用分离的大鼠胰岛、β-TC3细胞和T2 DM小鼠作为研究对象。结果表明，CHS通过促进间歇性高糖(IHG)诱导的β细胞增殖和减少细胞凋亡，恢复β细胞的分泌活性，促进β细胞存活。在体内，CHS保护胰岛β细胞的凋亡，使血糖正常化，改善糖尿病小鼠的胰岛素敏感性。进一步研究表明，CHS可激活WNT3a信号转导，抑制HBP1，促进β-连环素核转位，增强TCF7L2、GIPR和GLP-1R的表达，抑制p53、p27和p21的表达。在体外和在β-catenin(-/-)小鼠体内，siRNAs对TCF7L2或XAV-939(Wnt/β-catenin拮抗剂)的保护作用显著抑制。总之，我们确定了CHS通过激活Wnt3a/β-catenin/TCF7L2信号通路在保护β细胞存活和再生方面的新作用。提示CHS作为治疗2型糖尿病的干预药物具有潜在的应用价值。
Islet beta cell mass reduction induced by glucose fluctuation is crucial for the development and progression of T2DM. Chikusetsu saponin IVa (CHS) had protective effects against DM and related injuries. Here we aimed to investigate the role of CHS in beta cell injuries and its possible mechanism involved. Isolated rat islets, beta TC3 cells and T2DM mice were used in this study. The results showed that CHS restored the secretion activity, promoted beta cell survival by increasing beta cell proliferation and decreasing apoptosis which induced by intermittent high glucose (IHG). In vivo, CHS protected beta cell apoptosis to normalize blood glucose and improve insulin sensitivity in DM mice. Further studies showed that CHS activated Wnt3a signaling, inhibited HBP1, promoted beta-catenin nuclear translocation, enhanced expressions of TCF7L2, GIPR and GLP-1R, inhibited p53, p27 and p21. The protective effect of CHS was remarkably suppressed by siRNAs against TCF7L2 or XAV-939 (a Wnt/beta-catenin antagonist) in vitro and in beta-catenin(-/-) mice. In conclusion, we identified a novel role of CHS in protecting beta cell survival and regeneration by mechanisms involving the activation of Wnt3a/beta-catenin/TCF7L2 signaling. Our results indicated the potential value of CHS as a possible intervention drug for T2DM.