Cinnamtannin D1 Protects Pancreatic β-Cells from Glucolipotoxicity-Induced Apoptosis by Enhancement of Autophagy In Vitro and In Vivo.

Xin-Yi Wang, Bo-Rong Zhu, Qi Jia, Yi-Ming Li, Ting Wang, He-Yao Wang

Journal of agricultural and food chemistry 2020 Nov 11

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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 β 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 β-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 β-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.

Citation

Xin-Yi Wang, Bo-Rong Zhu, Qi Jia, Yi-Ming Li, Ting Wang, He-Yao Wang. Cinnamtannin D1 Protects Pancreatic β-Cells from Glucolipotoxicity-Induced Apoptosis by Enhancement of Autophagy In Vitro and In Vivo. Journal of agricultural and food chemistry. 2020 Nov 11;68(45):12617-12630