Chikusetsu saponin IVa protects pancreatic ß cell against intermittent high glucose-induced injury by activating Wnt/ß-catenin/TCF7L2 pathway.
Aging (Albany NY)
; 12(2): 1591-1609, 2020 01 22.
Article
en En
| MEDLINE
| ID: mdl-31969494
ABSTRACT
Islet ß 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 ß cell injuries and its possible mechanism involved. Isolated rat islets, ßTC3 cells and T2DM mice were used in this study. The results showed that CHS restored the secretion activity, promoted ß cell survival by increasing ß cell proliferation and decreasing apoptosis which induced by intermittent high glucose (IHG). In vivo, CHS protected ß cell apoptosis to normalize blood glucose and improve insulin sensitivity in DM mice. Further studies showed that CHS activated Wnt3a signaling, inhibited HBP1, promoted ß-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/ß-catenin antagonist) in vitro and in ß-catenin-/- mice. In conclusion, we identified a novel role of CHS in protecting ß cell survival and regeneration by mechanisms involving the activation of Wnt3a/ß-catenin/TCF7L2 signaling. Our results indicated the potential value of CHS as a possible intervention drug for T2DM.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ácido Oleanólico
/
Saponinas
/
Glucemia
/
Células Secretoras de Insulina
/
Proteína 2 Similar al Factor de Transcripción 7
/
Vía de Señalización Wnt
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Aging (Albany NY)
Asunto de la revista:
GERIATRIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China