PMID- 36030747
OWN - NLM
STAT- MEDLINE
DCOM- 20220926
LR  - 20220926
IS  - 1618-095X (Electronic)
IS  - 0944-7113 (Linking)
VI  - 106
DP  - 2022 Nov
TI  - Polydatin prevents lipotoxicity-induced dysfunction in pancreatic beta-cells by 
      inhibiting endoplasmic reticulum stress and excessive autophagy.
PG  - 154410
LID - S0944-7113(22)00499-8 [pii]
LID - 10.1016/j.phymed.2022.154410 [doi]
AB  - BACKGROUND: Chronically elevated free fatty acid levels can adversely affect 
      pancreatic beta-cells, leading to insulin resistance and eventually type 2 diabetes 
      mellitus (T2DM). Polydatin (PD) from Polygonum cuspidatum has been shown to 
      regulate blood lipid content and lower cholesterol levels. However, there have 
      been no reports on the potential therapeutic effects and actions of PD on 
      lipotoxicity in beta-cells. PURPOSE: This study aimed to investigate the protective 
      effects of PD on palmitate (PA)-treated INS-1 insulinoma cells and diabetic mice. 
      METHODS: Cells were incubated with PA and varying concentrations of PD for 24 h. 
      Viability assays, morphological observations, flow cytometric analysis, western 
      blotting, and reverse transcription-quantitative polymerase chain reaction were 
      used to assess the effects of PD on PA-induced lipotoxicity. Western blotting was 
      used to measure the endoplasmic reticulum stress (ERS) and the levels of 
      autophagy-related factors after incubation with inducers and inhibitors of ERS 
      and autophagy. Diabetic mice were treated with intragastric PD for 6 weeks 
      followed by the measurement of their physiological and blood lipid indices and 
      assessment of the results of histological and immunofluorescence analyses. 
      RESULTS: Treatment with PD after PA exposure enhanced insulin secretion and the 
      expression of diabetes-associated genes. PD promoted beta-cell function by reducing 
      the levels of proteins associated with ERS and autophagy while also attenuating 
      ERS triggered by tunicamycin. PD also reduced tunicamycin-induced autophagy, 
      indicating that it regulated ERS-mediated autophagy and reduced PA-induced 
      cellular dysfunction. In addition, treatment of db/db mice with PD substantially 
      reduced body weight gain, alleviated dyslipidemia, improved beta-cell function, and 
      reduced insulin resistance. CONCLUSION: These results suggest that PD protects 
      beta-cells from lipotoxicity-induced dysfunction and apoptosis by inhibiting ERS and 
      preventing excessive autophagy. Our study provides a new basis for exploring the 
      potential of PD against beta-cell lipotoxicity and T2DM.
CI  - Copyright (c) 2022 Elsevier GmbH. All rights reserved.
FAU - Jin, Wenqi
AU  - Jin W
AD  - Research Center of Traditional Chinese Medicine, the Affiliated Hospital to 
      Changchun University of Chinese Medicine, Changchun, China; College of pharmacy, 
      Changchun University of Chinese Medicine, Changchun, China.
FAU - Fan, Meiling
AU  - Fan M
AD  - Department of Obstetrics and Gynecology, Changchun University of Chinese 
      Medicine, Changchun, China.
FAU - Zhang, Yuxin
AU  - Zhang Y
AD  - Research Center of Traditional Chinese Medicine, the Affiliated Hospital to 
      Changchun University of Chinese Medicine, Changchun, China.
FAU - Zhang, Qi
AU  - Zhang Q
AD  - Research Center of Traditional Chinese Medicine, the Affiliated Hospital to 
      Changchun University of Chinese Medicine, Changchun, China.
FAU - Jing, Chenxu
AU  - Jing C
AD  - Research Center of Traditional Chinese Medicine, the Affiliated Hospital to 
      Changchun University of Chinese Medicine, Changchun, China.
FAU - Jiang, Rui
AU  - Jiang R
AD  - Research Center of Traditional Chinese Medicine, the Affiliated Hospital to 
      Changchun University of Chinese Medicine, Changchun, China.
FAU - Piao, Chunli
AU  - Piao C
AD  - Shenzhen Hospital, Guangzhou University of Chinese Medicine (Futian), Shenzhen, 
      China. Electronic address: pcl2013@sina.cn.
FAU - Sun, Liwei
AU  - Sun L
AD  - Research Center of Traditional Chinese Medicine, the Affiliated Hospital to 
      Changchun University of Chinese Medicine, Changchun, China; Jilin Provincial 
      Science and Technology Innovation Cross-regional Cooperation Center of 
      Traditional Chinese Medicine Health Product Research and Development, Changchun, 
      China. Electronic address: sunnylilwei@163.com.
LA  - eng
PT  - Journal Article
DEP - 20220820
PL  - Germany
TA  - Phytomedicine
JT  - Phytomedicine : international journal of phytotherapy and phytopharmacology
JID - 9438794
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Glucosides)
RN  - 0 (Palmitates)
RN  - 0 (Stilbenes)
RN  - 11089-65-9 (Tunicamycin)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - XM261C37CQ (polydatin)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Autophagy
MH  - Cholesterol/metabolism
MH  - *Diabetes Mellitus, Experimental/metabolism
MH  - *Diabetes Mellitus, Type 2/metabolism
MH  - Endoplasmic Reticulum Stress
MH  - Fatty Acids, Nonesterified/metabolism
MH  - Glucosides
MH  - *Insulin Resistance
MH  - *Insulin-Secreting Cells
MH  - Mice
MH  - Palmitates/metabolism/toxicity
MH  - Stilbenes
MH  - Tunicamycin
OTO - NOTNLM
OT  - Autophagy
OT  - Endoplasmic reticulum stress
OT  - Lipotoxicity
OT  - Polydatin
OT  - beta-Cell function
COIS- Declaration of Competing Interest The authors declare no competing financial 
      interests.
EDAT- 2022/08/29 06:00
MHDA- 2022/09/28 06:00
CRDT- 2022/08/28 18:21
PHST- 2022/03/12 00:00 [received]
PHST- 2022/08/13 00:00 [revised]
PHST- 2022/08/19 00:00 [accepted]
PHST- 2022/08/29 06:00 [pubmed]
PHST- 2022/09/28 06:00 [medline]
PHST- 2022/08/28 18:21 [entrez]
AID - S0944-7113(22)00499-8 [pii]
AID - 10.1016/j.phymed.2022.154410 [doi]
PST - ppublish
SO  - Phytomedicine. 2022 Nov;106:154410. doi: 10.1016/j.phymed.2022.154410. Epub 2022 
      Aug 20.