PMID- 30841431
OWN - NLM
STAT- MEDLINE
DCOM- 20190621
LR  - 20190621
IS  - 1950-6007 (Electronic)
IS  - 0753-3322 (Linking)
VI  - 111
DP  - 2019 Mar
TI  - Novel protective effect of O-1602 and abnormal cannabidiol, GPR55 agonists, on ER 
      stress-induced apoptosis in pancreatic beta-cells.
PG  - 1176-1186
LID - S0753-3322(18)37566-8 [pii]
LID - 10.1016/j.biopha.2018.12.126 [doi]
AB  - Insulin resistance and beta-cell dysfunction are the main defects in Type 2 Diabetes 
      Mellitus (T2DM), and beta-cell dysfunction and apoptosis is the critical determinant 
      in the progression of T2DM. G-protein coupled receptor 55 (GPR55) is an orphan 
      G-protein coupled receptor, which is activated by endocannabinoids and lipid 
      transmitters. Recently, GPR55 was shown to regulate glucose and energy 
      homeostasis, however its role in beta-cell apoptosis was not studied. Therefore, in 
      this study, we investigated the novel effect of GPR55 agonists, O-1602 and 
      abnormal cannabidiol (Abn-CBD), on endoplasmic reticulum (ER) stress-induced 
      apoptosis in mouse pancreatic beta-cell lines, MIN6 and Beta-TC-6, and its 
      underlying mechanisms. Our results showed that O-1602 and Abn-CBD reduced ER 
      stress-induced apoptosis in MIN6 and Beta-TC-6 cells. This was through the 
      phosphorylation of 3'-5'-cyclic adenosine monophosphate response element-binding 
      protein (CREB) in beta-cells, hence activating CREB downstream anti-apoptotic genes, 
      Bcl-2 and Bcl-xL. Moreover, O-1602 and Abn-CBD directly activated kinases, 
      CaMKIV, Erk1/2 and PKA, to induce CREB phosphorylation. Therefore, our results 
      indicated that GPR55 agonists protected from beta-cell apoptosis through CREB 
      activation, thus up-regulating anti-apoptotic genes. In conclusion, our study 
      provided a novel protective effect of GPR55 agonists on ER stress-induced 
      apoptosis in beta-cells and its underlying mechanisms mediating this protection, 
      therefore we suggested that GPR55 might be a therapeutic target for T2DM.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Masson SAS.. All rights 
      reserved.
FAU - Vong, Chi Teng
AU  - Vong CT
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, 
      Macau, China.
FAU - Tseng, Hisa Hui Ling
AU  - Tseng HHL
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, 
      Macau, China.
FAU - Kwan, Yiu Wa
AU  - Kwan YW
AD  - School of Biomedical Sciences, Faculty of Medicine, The Chinese University of 
      Hong Kong, Shatin, N.T., Hong Kong, China.
FAU - Lee, Simon Ming-Yuen
AU  - Lee SM
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, 
      Macau, China.
FAU - Hoi, Maggie Pui Man
AU  - Hoi MPM
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, 
      Macau, China. Electronic address: maghoi@umac.mo.
LA  - eng
PT  - Journal Article
DEP - 20190115
PL  - France
TA  - Biomed Pharmacother
JT  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
JID - 8213295
RN  - 0 (GPR55 protein, mouse)
RN  - 0 (Protective Agents)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Receptors, Cannabinoid)
RN  - 0 (bcl-X Protein)
RN  - 19GBJ60SN5 (Cannabidiol)
RN  - 317321-41-8 (O-1602 compound)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Cannabidiol/*analogs & derivatives/*pharmacology
MH  - Cell Line
MH  - Diabetes Mellitus, Type 2/drug therapy/metabolism
MH  - Endoplasmic Reticulum/drug effects/metabolism
MH  - Endoplasmic Reticulum Stress/*drug effects
MH  - Insulin-Secreting Cells/*drug effects/metabolism
MH  - MAP Kinase Signaling System/drug effects
MH  - Mice
MH  - Phosphorylation/drug effects
MH  - Protective Agents/*pharmacology
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Receptors, Cannabinoid/*metabolism
MH  - Signal Transduction/drug effects
MH  - Up-Regulation/drug effects
MH  - bcl-X Protein/metabolism
OTO - NOTNLM
OT  - CREB
OT  - ER stress
OT  - GPR55
OT  - beta-Cell apoptosis
EDAT- 2019/03/08 06:00
MHDA- 2019/06/22 06:00
CRDT- 2019/03/08 06:00
PHST- 2018/10/21 00:00 [received]
PHST- 2018/12/27 00:00 [revised]
PHST- 2018/12/30 00:00 [accepted]
PHST- 2019/03/08 06:00 [entrez]
PHST- 2019/03/08 06:00 [pubmed]
PHST- 2019/06/22 06:00 [medline]
AID - S0753-3322(18)37566-8 [pii]
AID - 10.1016/j.biopha.2018.12.126 [doi]
PST - ppublish
SO  - Biomed Pharmacother. 2019 Mar;111:1176-1186. doi: 10.1016/j.biopha.2018.12.126. 
      Epub 2019 Jan 15.