Research Paper Volume 12, Issue 2 pp 1591—1609
Chikusetsu saponin IVa protects pancreatic β cell against intermittent high glucose-induced injury by activating Wnt/β-catenin/TCF7L2 pathway
- 1 Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China
- 2 Department of Chinese Medicine, School of Life Science, Northwestern University, Xi’an 710032, Shaanxi, China
- 3 Department of Pharmacy, Chongqing Dazu District Hospital of Traditional Chinese Medicine, Chongqing 402360, China
Received: November 13, 2019 Accepted: December 27, 2019 Published: January 22, 2020
https://doi.org/10.18632/aging.102702How to Cite
Abstract
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.