PMID- 32005067
OWN - NLM
STAT- MEDLINE
DCOM- 20201027
LR  - 20201027
IS  - 2224-5839 (Electronic)
IS  - 2224-5820 (Linking)
VI  - 9
IP  - 1
DP  - 2020 Jan
TI  - Emulsified isoflurane protects beta cells against high glucose-induced apoptosis 
      via inhibiting endoplasmic reticulum stress.
PG  - 90-97
LID - 10.21037/apm.2019.11.31 [doi]
AB  - BACKGROUND: Pancreatic beta cell damage induced by glucose toxicity is an 
      important factor in type 2 diabetes mellitus (T2DM). It has become evident that 
      endoplasmic reticulum stress (ERS)-induced apoptosis was contributed to beta cell 
      dysfunction and insulin resistance. Our previous work showed that emulsified 
      isoflurane (EIso) could alleviate ERS in lung reperfusion injury. This study 
      aimed to elucidate whether EIso could alleviate apoptosis induced by glucose in 
      rat islet RIN-m5F beta cells via inhibiting ERS. METHODS: RIN-m5F cells were 
      divided into five groups: the control group; the 0.1G group, cultured in 0.1M 
      glucose for 24 h; the 0.3G group, cultured in 0.3M glucose for 24 h; the 0.3G + 
      57E group, cultured in 0.3M glucose with 57 microM EIso for 24 h, and the 0.3G + 76E 
      group, cultured in 0.3M glucose with 76 microM EIso for 24 h. First, cell 
      proliferation was measured by MTT assay, and the level of insulin secretion was 
      measured with enzyme-linked immunosorbent assay (ELISA) kit. Second, the 
      expression of B cell leukemia/lymphoma 2 (Bcl-2) associated X (Bax) and Bcl-2 
      were detected by Western blotting. The level of caspase-3 activity was assessed 
      by colorimetric method. Finally, the ERS marker CHOP and GRP78 expression were 
      detected by Western blotting. The levels of activating transcription factor-6 
      (ATF6), X-box-binding protein 1 (Xbp1), and eukaryotic translation initiation 
      factor-2alpha (eIF2alpha) mRNA were assessed by quantitative real-time polymerase chain 
      reaction (qRT-PCR) after being treated with EIso for 24 h. RESULTS: We found that 
      exposure to high glucose reduced RIN-m5F cell viability, stimulated the secretion 
      of insulin, activated caspase-3, improved the expression of Bax, and 
      down-regulated Bcl-2. EIso improved the survival and protected the function of 
      RIN-m5F. Compared to the 0.3G group, treatment with EIso inhibited the activity 
      of caspase-3, and decreased the expression of Bax. The expression of CHOP and 
      GRP78 were significantly suppressed by EIso at 24 h in a dose-dependent manner. 
      The level of ATF6, Xbp1, and eIF2alpha mRNA of RIN-m5F were enhanced by high glucose, 
      but only eIF2alpha mRNA was significantly decreased by EIso treatment. CONCLUSIONS: 
      The present study suggests that high glucose induces rat islet beta cell RIN-m5F 
      apoptosis and aggravates the function of beta cells. EIso protects beta cells 
      against high glucose through the ERS-dependent apoptotic pathway and might serve 
      as a potential therapy for diabetes.
FAU - Yang, Zhenkun
AU  - Yang Z
AD  - Center of Clinical Research, Wuxi People's Hospital of Nanjing Medical 
      University, Wuxi 214023, China.
FAU - Wu, Shuoxiong
AU  - Wu S
AD  - Department of Anesthesiology, Wuxi Children's Hospital, Wuxi 214023, China.
FAU - Zhao, Jingjing
AU  - Zhao J
AD  - Center of Clinical Research, Wuxi People's Hospital of Nanjing Medical 
      University, Wuxi 214023, China.
FAU - Wang, Zuoyu
AU  - Wang Z
AD  - Department of Medical Oncology, Wuxi People's Hospital of Nanjing Medical 
      University, Wuxi 214023, China.
FAU - Yao, Min
AU  - Yao M
AD  - Department of Anesthesiology, Wuxi Children's Hospital, Wuxi 214023, China.
FAU - Lu, Peihua
AU  - Lu P
AD  - Department of Medical Oncology, Wuxi People's Hospital of Nanjing Medical 
      University, Wuxi 214023, China.
FAU - Dong, Wenyan
AU  - Dong W
AD  - Department of Anesthesiology, Wuxi Children's Hospital, Wuxi 214023, China. 
      wxdongwenyan@163.com.
FAU - Sun, Jie
AU  - Sun J
AD  - Center of Clinical Research, Wuxi People's Hospital of Nanjing Medical 
      University, Wuxi 214023, China. sunjie0220@njmu.edu.cn.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Palliat Med
JT  - Annals of palliative medicine
JID - 101585484
RN  - 0 (Anesthetics, Inhalation)
RN  - 0 (Emulsions)
RN  - CYS9AKD70P (Isoflurane)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Anesthetics, Inhalation/*pharmacology
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Emulsions
MH  - Endoplasmic Reticulum Stress/*drug effects
MH  - Glucose/*administration & dosage
MH  - Insulin-Secreting Cells/cytology/*drug effects
MH  - Isoflurane/*pharmacology
MH  - Rats
OTO - NOTNLM
OT  - Emulsified isoflurane (EIso)
OT  - apoptosis
OT  - endoplasmic reticulum stress (ERS)
OT  - glucotoxicity
OT  - islet beta cell
EDAT- 2020/02/02 06:00
MHDA- 2020/10/28 06:00
CRDT- 2020/02/02 06:00
PHST- 2019/11/04 00:00 [received]
PHST- 2019/11/29 00:00 [accepted]
PHST- 2020/02/02 06:00 [entrez]
PHST- 2020/02/02 06:00 [pubmed]
PHST- 2020/10/28 06:00 [medline]
AID - 10.21037/apm.2019.11.31 [doi]
PST - ppublish
SO  - Ann Palliat Med. 2020 Jan;9(1):90-97. doi: 10.21037/apm.2019.11.31.