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Cinnamtannin D1 Protects Pancreatic beta-Cells from Glucolipotoxicity-Induced Apoptosis by Enhancement of Autophagy In Vitro and In Vivo
Wang, Xin-Yi1,2; Zhu, Bo-Rong3; Jia, Qi3; Li, Yi-Ming3; Wang, Ting2; Wang, He-Yao1,2
刊名JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
2020-11-11
卷号68期号:45页码:12617-12630
关键词cinnamtannin D1 pancreatic beta-cells autophagy apoptosis type 2 diabetes
ISSN号0021-8561
DOI10.1021/acs.jafc.0c04898
通讯作者Li, Yi-Ming(ymlius@163.com) ; Wang, Ting(zhenwojingcaihaha@126.com) ; Wang, He-Yao(hywang@simm.ac.cn)
英文摘要In our previous study, cinnamtannin D1 (CD-1), one of the A-type procyanidin oligomers isolated from Cinnamomum tamala, was reported to have the activity of antiapoptosis in palmitic acid-treated pancreatic beta cells via alleviating oxidative stress in vitro. In this study, the aim was to further disclose its protective effect and underlying mechanisms against glucolipotoxicity-induced beta-cells apoptosis in vitro and in vivo. We found that CD-1 was able to dose-dependently and time-dependently activate autophagy in INS-1 pancreatic beta-cells. High glucose and palmitic acid (HG/PA)-induced apoptosis and autophagy impairment could be attenuated by CD-1 in INS-1 cells as well as primary cultured murine islets. We also demonstrated that CD-1-induced autophagy was through AMPK/mTOR/ULK1 pathway. Moreover, it was shown that the effects of CD-1 on activation of Keap1/Nrf2 antioxidant signaling pathway and the amelioration of inflammation, endoplasmic reticulum stress, and apoptosis were through autophagy induction in HG/PA-treated INS-1 cells. These protective effects in vivo and hypoglycemic activity of CD-1 were also observed in diabetic db/db mice. These findings have great significance in revealing the antidiabetic mechanisms of procyanidin oligomers and paving the way for their application in the treatment of diabetes.
资助项目National Natural Science Foundation of China[81773791] ; State Key Laboratory of Drug Research[SIMM2004KF-06] ; State Key Laboratory of Phytochemistry and Plant Resources in West China[P2018-KF04] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002-002-007] ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12040336]
WOS研究方向Agriculture ; Chemistry ; Food Science & Technology
语种英语
出版者AMER CHEMICAL SOC
WOS记录号WOS:000592487700011
内容类型期刊论文
源URL[http://119.78.100.183/handle/2S10ELR8/296109]  
专题中国科学院上海药物研究所
通讯作者Li, Yi-Ming; Wang, Ting; Wang, He-Yao
作者单位1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714
Wang, Xin-Yi,Zhu, Bo-Rong,Jia, Qi,et al. Cinnamtannin D1 Protects Pancreatic beta-Cells from Glucolipotoxicity-Induced Apoptosis by Enhancement of Autophagy In Vitro and In Vivo[J]. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY,2020,68(45):12617-12630.
APA Wang, Xin-Yi,Zhu, Bo-Rong,Jia, Qi,Li, Yi-Ming,Wang, Ting,&Wang, He-Yao.(2020).Cinnamtannin D1 Protects Pancreatic beta-Cells from Glucolipotoxicity-Induced Apoptosis by Enhancement of Autophagy In Vitro and In Vivo.JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY,68(45),12617-12630.
MLA Wang, Xin-Yi,et al."Cinnamtannin D1 Protects Pancreatic beta-Cells from Glucolipotoxicity-Induced Apoptosis by Enhancement of Autophagy In Vitro and In Vivo".JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 68.45(2020):12617-12630.
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