Xiaokeping-induced autophagy protects pancreatic β-cells against apoptosis under high glucose stress

• Published in: Biomedicine & pharmacotherapy 2018-09, Vol.105, p.407-412
• Main Authors: Wu, Yanyang, Hu, Yongquan, Haiyan, Zhou, YunLin, Wei, Xincong, Kang, Dongbo, Liu
• Format: Article
• Language: English
• Subjects: Apoptosis; Autophagy; High glucose; β-cells
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.05.147

[Display omitted] •XKP protects MIN-6 cells against high glucose induced apoptosis.•XKP induces autophagy via mTOR pathway.•This induction of autophagy protects MIN-6 cells from apoptosis and maintains the mass of β-cells. Based on the cytoprotective effects of autophagy, up-regulation of autophagy to enhancing β-cells surviving may be a potential therapeutic target. Xiaokeping (XKP), a prescribed Traditional Chinese Medicine (TCM), has been used to treat patients with type Ⅱ diabetes mellitus for many years; however, the molecular mechanism of its effects is unknown. As the only insulin producer, the pancreatic β cell plays an important role in diabetes. Whether XKP influences the viability of pancreatic β cells remains to be substantiated. In the present study, autophagy/apoptosis analyses were used to evaluate the therapeutic effect of XKP on pancreatic β-cells induced by high glucose levels and to investigate a potential causal molecular mechanism of XKP effect on the cells. The pancreatic β-cell lines MIN-6 were divided into four groups: control, high glucose (33.3 mmol/L), high glucose with XKP, high glucose with XKP and 3-Methyladenine (3-MA). Immunofluorescence assay was employed to determine autophagosome formation and flow cytometry was used to determine apoptotic rates of the β cells by the detecting expression of autophagy- and apoptosis-related proteins. High glucose increased the apoptotic rate of β-cells from 5.37% to 23.24%; however addition of XKP mitigated the rate at 10.92%. Data indicate that autophagy of β-cells was induced by XKP via the mammalian target of rapamycin (mTOR) pathway. Where the autophagy inhibitor 3-MA was added, the apoptotic rate was 23.94%, similar to the high glucose group rate. The results suggest a potential cytoprotective effect of XKP from high glucose toxicity by its induction of autophagy which may be linked to mTOR-mediated autophagy.