PMID- 32275937
OWN - NLM
STAT- MEDLINE
DCOM- 20200601
LR  - 20200601
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 252
DP  - 2020 Jul 1
TI  - Liraglutide protects pancreatic beta cells from endoplasmic reticulum stress by 
      upregulating MANF to promote autophagy turnover.
PG  - 117648
LID - S0024-3205(20)30396-9 [pii]
LID - 10.1016/j.lfs.2020.117648 [doi]
AB  - AIMS: This study was conducted to determine the relationship between 
      mesencephalic astrocyte-derived neurotrophic factor (MANF), autophagy and 
      endoplasmic reticulum (ER) stress, and whether liraglutide (LRG) can protect beta 
      cells, promote autophagy and alleviate ER stress by regulating MANF expression. 
      MAIN METHODS: Human serum samples were collected from healthy controls (NC), 
      simple hyperlipidemia (HLD), and newly diagnosed type 2 diabetes (T2D). The MANF 
      levels were detected using ELISA. In vitro, after the mouse islet MIN6 cells were 
      treated with glucose (GLU), palmitate (PA), thapsigargin (TG), LRG, and 
      chloroquine (CQ), cell proliferation was detected using cell counting kit-8 
      (CCK-8), apoptosis-related protein cleaved caspase 3 (C-cas-3), ER stress, and 
      autophagy-related proteins were detected by Western blotting, MANF, insulin, and 
      C-cas-3 proteins were detected via immunofluorescence. Subcellular structures and 
      autophagosomes were examined using electron microscopy. KEY FINDINGS: Compared 
      with the NC group, the MANF levels in the HLD and T2D groups increased 
      significantly. After ER stress induced by GLU, PA, and TG, cell viability 
      decreased, while MANF, c-cas3, ERS, and autophagy-related proteins increased, 
      which was related to the concentration of GLU, PA, and TG. Compared with the BSA 
      group, the number of mitochondria and autophagosomes in the PA group increased 
      and the mitochondria were damaged. In the PA and TG plus CQ groups, the effect 
      was further exaggerated. But after co-treatment with LRG, the effects of GLU, PA, 
      and TG were attenuated. SIGNIFICANCE: LRG protects islet beta cells from ER stress 
      by upregulating MANF to promote autophagy turnover.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Fu, Jili
AU  - Fu J
AD  - Department of Endocrinology and Metabolism, The Second Affiliated Hospital of 
      Chongqing Medical University, 76, Linjiang Road, Yuzhong District, Chongqing 
      400010, China.
FAU - Nchambi, Kija Malale
AU  - Nchambi KM
AD  - Department of Gastroenterology, The Second Affiliated Hospital of Chongqing 
      Medical University, 76, Linjiang Road, Yuzhong District, Chongqing 400010, China.
FAU - Wu, Hao
AU  - Wu H
AD  - Department of Hepatobiliary surgery, The Second Affiliated Hospital of Chongqing 
      Medical University, 76, Linjiang Road, Yuzhong District, Chongqing 400010, China.
FAU - Luo, Xie
AU  - Luo X
AD  - Department of Endocrinology and Metabolism, The Second Affiliated Hospital of 
      Chongqing Medical University, 76, Linjiang Road, Yuzhong District, Chongqing 
      400010, China.
FAU - An, Xizhou
AU  - An X
AD  - Department of Hematology, The Children Hospital of Chongqing Medical University, 
      Yuzhong District, Chongqing 400014, China.
FAU - Liu, Dongfang
AU  - Liu D
AD  - Department of Endocrinology and Metabolism, The Second Affiliated Hospital of 
      Chongqing Medical University, 76, Linjiang Road, Yuzhong District, Chongqing 
      400010, China. Electronic address: 300306@hospital.cqmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20200408
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (MANF protein, human)
RN  - 0 (Nerve Growth Factors)
RN  - 839I73S42A (Liraglutide)
SB  - IM
MH  - Animals
MH  - Autophagy/*drug effects
MH  - Cell Survival/drug effects
MH  - Diabetes Mellitus, Type 2/drug therapy
MH  - Endoplasmic Reticulum Stress/*drug effects
MH  - Humans
MH  - Hyperlipidemias/drug therapy
MH  - Hypoglycemic Agents/pharmacology
MH  - Insulin-Secreting Cells/*drug effects/metabolism
MH  - Liraglutide/*pharmacology
MH  - Mice
MH  - Nerve Growth Factors/*genetics
MH  - Up-Regulation/drug effects
OTO - NOTNLM
OT  - Autophagy
OT  - Endoplasmic reticulum stress
OT  - Liraglutide
OT  - MANF
OT  - beta cells
COIS- Declaration of competing interest The authors declare that there are no conflicts 
      of interest.
EDAT- 2020/04/11 06:00
MHDA- 2020/06/02 06:00
CRDT- 2020/04/11 06:00
PHST- 2020/01/09 00:00 [received]
PHST- 2020/03/31 00:00 [revised]
PHST- 2020/04/05 00:00 [accepted]
PHST- 2020/04/11 06:00 [pubmed]
PHST- 2020/06/02 06:00 [medline]
PHST- 2020/04/11 06:00 [entrez]
AID - S0024-3205(20)30396-9 [pii]
AID - 10.1016/j.lfs.2020.117648 [doi]
PST - ppublish
SO  - Life Sci. 2020 Jul 1;252:117648. doi: 10.1016/j.lfs.2020.117648. Epub 2020 Apr 8.