PMID- 30523046
OWN - NLM
STAT- MEDLINE
DCOM- 20191022
LR  - 20191210
IS  - 1470-8736 (Electronic)
IS  - 0143-5221 (Linking)
VI  - 133
IP  - 1
DP  - 2019 Jan 15
TI  - GPR120 protects lipotoxicity-induced pancreatic beta-cell dysfunction through 
      regulation of PDX1 expression and inhibition of islet inflammation.
PG  - 101-116
LID - 10.1042/CS20180836 [doi]
AB  - G-protein coupled receptor 120 (GPR120) has been shown to act as an omega-3 
      unsaturated fatty acid sensor and is involved in insulin secretion. However, the 
      underlying mechanism in pancreatic beta cells remains unclear. To explore the 
      potential link between GPR120 and beta-cell function, its agonists docosahexaenoic 
      acid (DHA) and GSK137647A were used in palmitic acid (PA)-induced pancreatic 
      beta-cell dysfunction, coupled with GPR120 knockdown (KD) in MIN6 cells and GPR120 
      knockout (KO) mice to identify the underlying signaling pathways. In vitro and ex 
      vivo treatments of MIN6 cells and islets isolated from wild-type (WT) mice with 
      DHA and GSK137647A restored pancreatic duodenal homeobox-1 (PDX1) expression 
      levels and beta-cell function via inhibiting PA-induced elevation of proinflammatory 
      chemokines and activation of nuclear factor kappaB, c-Jun amino (N)-terminal 
      kinases1/2 and p38MAPK signaling pathways. On the contrary, these GPR120 
      agonism-mediated protective effects were abolished in GPR120 KD cells and islets 
      isolated from GPR120 KO mice. Furthermore, GPR120 KO mice displayed glucose 
      intolerance and insulin resistance relative to WT littermates, and beta-cell 
      functional related genes were decreased while inflammation was exacerbated in 
      islets with increased macrophages in pancreas from GPR120 KO mice. DHA and 
      GSK137647A supplementation ameliorated glucose tolerance and insulin sensitivity, 
      as well as improved Pdx1 expression and islet inflammation in diet-induced obese 
      WT mice, but not in GPR120 KO mice. These findings indicate that GPR120 
      activation is protective against lipotoxicity-induced pancreatic beta-cell 
      dysfunction, via the mediation of PDX1 expression and inhibition of islet 
      inflammation, and that GPR120 activation may serve as a preventative and 
      therapeutic target for obesity and diabetes.
CI  - (c) 2019 The Author(s). Published by Portland Press Limited on behalf of the 
      Biochemical Society.
FAU - Wang, Yi
AU  - Wang Y
AD  - School of Biomedical Sciences, Faculty of Medicine, The Chinese University of 
      Hong Kong, Shatin, Hong Kong, China.
FAU - Xie, Ting
AU  - Xie T
AD  - School of Biomedical Sciences, Faculty of Medicine, The Chinese University of 
      Hong Kong, Shatin, Hong Kong, China.
FAU - Zhang, Dan
AU  - Zhang D
AD  - School of Biomedical Sciences, Faculty of Medicine, The Chinese University of 
      Hong Kong, Shatin, Hong Kong, China.
FAU - Leung, Po Sing
AU  - Leung PS
AUID- ORCID: 0000-0001-8074-3178
AD  - School of Biomedical Sciences, Faculty of Medicine, The Chinese University of 
      Hong Kong, Shatin, Hong Kong, China psleung@cuhk.edu.hk.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190111
PL  - England
TA  - Clin Sci (Lond)
JT  - Clinical science (London, England : 1979)
JID - 7905731
RN  - 0 (Aniline Compounds)
RN  - 0 (Blood Glucose)
RN  - 0 (Cytokines)
RN  - 0 (FFAR4 protein, mouse)
RN  - 0 (GSK137647)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Insulin)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Sulfonamides)
RN  - 0 (Trans-Activators)
RN  - 0 (pancreatic and duodenal homeobox 1 protein)
RN  - 25167-62-8 (Docosahexaenoic Acids)
RN  - 2V16EO95H1 (Palmitic Acid)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Aniline Compounds/pharmacology
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Cell Line, Tumor
MH  - Cytokines/metabolism
MH  - *Diet, High-Fat
MH  - Disease Models, Animal
MH  - Docosahexaenoic Acids/pharmacology
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Homeodomain Proteins/genetics/*metabolism
MH  - Inflammation Mediators/metabolism
MH  - Insulin/blood
MH  - Insulin-Secreting Cells/*drug effects/metabolism/pathology
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Palmitic Acid/*toxicity
MH  - Pancreatitis/etiology/metabolism/pathology/*prevention & control
MH  - Receptors, G-Protein-Coupled/agonists/deficiency/genetics/*metabolism
MH  - Signal Transduction/drug effects
MH  - Sulfonamides/pharmacology
MH  - Trans-Activators/genetics/*metabolism
OTO - NOTNLM
OT  - CCL2
OT  - CXCL1
OT  - DHA
OT  - FFAR4
OT  - GSK137647AS
OT  - Palmitic acid
EDAT- 2018/12/14 06:00
MHDA- 2019/10/23 06:00
CRDT- 2018/12/08 06:00
PHST- 2018/09/27 00:00 [received]
PHST- 2018/11/29 00:00 [revised]
PHST- 2018/12/05 00:00 [accepted]
PHST- 2018/12/14 06:00 [pubmed]
PHST- 2019/10/23 06:00 [medline]
PHST- 2018/12/08 06:00 [entrez]
AID - CS20180836 [pii]
AID - 10.1042/CS20180836 [doi]
PST - epublish
SO  - Clin Sci (Lond). 2019 Jan 11;133(1):101-116. doi: 10.1042/CS20180836. Print 2019 
      Jan 15.