PMID- 38367173
OWN - NLM
STAT- Publisher
LR  - 20240217
IS  - 1559-0720 (Electronic)
IS  - 0163-4984 (Linking)
DP  - 2024 Feb 17
TI  - Grape Seed Proanthocyanidins Protect Pancreatic beta Cells Against Ferroptosis via 
      the Nrf2 Pathway in Type 2 Diabetes.
LID - 10.1007/s12011-024-04093-9 [doi]
AB  - Pancreatic beta cell damage is the primary contributor to type 2 diabetes mellitus 
      (T2DM); however, the underlying mechanism remains nebulous. This study explored 
      the role of ferroptosis in pancreatic beta cell damage and the protective effects of 
      grape seed proanthocyanidin extract (GSPE). In T2DM model rats, the blood 
      glucose, water intake, urine volume, HbA1c, and homeostasis model 
      assessment-insulin resistance were significantly increased, while the body weight 
      and the insulin level were significantly decreased, indicating the successful 
      establishment of the T2DM model. MIN6 mouse insulinoma beta cells were cultured in 
      high glucose and sodium palmitate conditions to obtain a glycolipid damage model, 
      which was administered with GSPE, ferrostatin-1 (Fer-1), or nuclear factor 
      erythroid 2-related factor 2 (Nrf2) small interfering (si) RNA. GSPE and Fer-1 
      treatment significantly improved pancreatic beta-cell dysfunction and protected 
      against cell death. Both treatments increased the superoxide dismutase and 
      glutathione activity, reduced the malondialdehyde and reactive oxygen species 
      levels, and improved iron metabolism. Furthermore, the treatments reversed the 
      expression of ferroptosis markers cysteine/glutamate transporter (XCT) and 
      glutathione peroxidase 4 (GPX4) caused by glycolipid toxicity. GSPE treatments 
      activated the expression of Nrf2 and related proteins. These effects were 
      reversed when co-transfected with si-Nrf2. GSPE inhibits ferroptosis by 
      activating the Nrf2 signaling pathway, thus reducing beta-cell damage and 
      dysfunction in T2DM. Therefore, GSPE is a potential treatment strategy against 
      T2DM.
CI  - (c) 2024. The Author(s).
FAU - Li, Haiyan
AU  - Li H
AD  - Key Laboratory of Environmental Exposome, Xinjiang Medical University, No.393 
      Xinyi Road, Urumqi, 830011, China.
AD  - Department of Public Health, Shihezi University School of Medicine, Shihezi, 
      832000, China.
FAU - Zhang, Haowei
AU  - Zhang H
AD  - School of Exercise Science, Physical and Health Education, University of 
      Victoria, Victoria, BC, V8P 5C2, Canada.
FAU - Wang, Tongling
AU  - Wang T
AD  - Department of Public Health, Shihezi University School of Medicine, Shihezi, 
      832000, China.
FAU - Zhang, Liyuan
AU  - Zhang L
AD  - Department of Public Health, Shihezi University School of Medicine, Shihezi, 
      832000, China.
FAU - Wang, Hao
AU  - Wang H
AD  - Department of Public Health, Shihezi University School of Medicine, Shihezi, 
      832000, China.
FAU - Lu, Heng
AU  - Lu H
AD  - Department of Public Health, Shihezi University School of Medicine, Shihezi, 
      832000, China.
FAU - Yang, Ruirui
AU  - Yang R
AD  - Department of Public Health, Shihezi University School of Medicine, Shihezi, 
      832000, China.
FAU - Ding, Yusong
AU  - Ding Y
AD  - Key Laboratory of Environmental Exposome, Xinjiang Medical University, No.393 
      Xinyi Road, Urumqi, 830011, China. 51603030@qq.com.
LA  - eng
GR  - No. 2021AB030/the Science and Technology Project of Xinjiang Production and 
      onstruction Corps/
GR  - No. 2021AB030/the Science and Technology Project of Xinjiang Production and 
      onstruction Corps/
GR  - No. 2021AB030/the Science and Technology Project of Xinjiang Production and 
      onstruction Corps/
GR  - No. 2021AB030/the Science and Technology Project of Xinjiang Production and 
      onstruction Corps/
PT  - Journal Article
DEP - 20240217
PL  - United States
TA  - Biol Trace Elem Res
JT  - Biological trace element research
JID - 7911509
SB  - IM
OTO - NOTNLM
OT  - Diabetes mellitus
OT  - Ferroptosis
OT  - GSPE
OT  - Iron overload
OT  - NF-E2-related factor 2
OT  - Type 2
EDAT- 2024/02/17 21:43
MHDA- 2024/02/17 21:43
CRDT- 2024/02/17 11:09
PHST- 2023/08/24 00:00 [received]
PHST- 2024/02/01 00:00 [accepted]
PHST- 2024/02/17 21:43 [medline]
PHST- 2024/02/17 21:43 [pubmed]
PHST- 2024/02/17 11:09 [entrez]
AID - 10.1007/s12011-024-04093-9 [pii]
AID - 10.1007/s12011-024-04093-9 [doi]
PST - aheadofprint
SO  - Biol Trace Elem Res. 2024 Feb 17. doi: 10.1007/s12011-024-04093-9.