Chikusetsu saponin IVa protects pancreatic β cell against intermittent high glucose-induced injury by activating Wnt/β-catenin/TCF7L2 pathway | Zendy

Jia Cui | Zendy; Jialin Duan | Zendy; Jianjie Chu | Zendy; Chao Guo | Zendy; Miaomiao Xi | Zendy; Yi Li | Zendy; Yan Weng | Zendy; Wei Guo | Zendy; Ying Yin | Zendy; Aidong Wen | Zendy; Boling Qiao | Zendy

Open Access

Chikusetsu saponin IVa protects pancreatic β cell against intermittent high glucose-induced injury by activating Wnt/β-catenin/TCF7L2 pathway

Author(s) -

Jia Cui,

Jialin Duan,

Jianjie Chu,

Chao Guo,

Miaomiao Xi,

Yi Li,

Yan Weng,

Wei Guo,

Ying Yin,

Aidong Wen,

Boling Qiao

Publication year - 2020

Publication title -

aging

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.473

H-Index - 90

ISSN - 1945-4589

DOI - 10.18632/aging.102702

Subject(s) - wnt signaling pathway , saponin , catenin , microbiology and biotechnology , chemistry , tcf7l2 , pharmacology , medicine , signal transduction , biology , biochemistry , pathology , alternative medicine , genotype , single nucleotide polymorphism , gene

Islet β 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 β cell injuries and its possible mechanism involved. Isolated rat islets, βTC3 cells and T2DM mice were used in this study. The results showed that CHS restored the secretion activity, promoted β cell survival by increasing β cell proliferation and decreasing apoptosis which induced by intermittent high glucose (IHG). In vivo , CHS protected β cell apoptosis to normalize blood glucose and improve insulin sensitivity in DM mice. Further studies showed that CHS activated Wnt3a signaling, inhibited HBP1, promoted β-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/β-catenin antagonist) in vitro and in β-catenin -/- mice. In conclusion, we identified a novel role of CHS in protecting β cell survival and regeneration by mechanisms involving the activation of Wnt3a/β-catenin/TCF7L2 signaling. Our results indicated the potential value of CHS as a possible intervention drug for T2DM.

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