PMID- 31364177
OWN - NLM
STAT- MEDLINE
DCOM- 20200513
LR  - 20200513
IS  - 1558-9307 (Electronic)
IS  - 0024-4201 (Linking)
VI  - 54
IP  - 10
DP  - 2019 Oct
TI  - Activated PPARbeta/delta Protects Pancreatic beta Cells in Type 2 Diabetic Goto-Kakizaki 
      Rats from Lipoapoptosis via GPR40.
PG  - 603-616
LID - 10.1002/lipd.12182 [doi]
AB  - GW501516-activated peroxisome proliferator-activated receptor (PPAR) beta/delta and 
      G-protein-coupled receptor (GPR) 40 were shown to protect pancreatic beta cells 
      against lipoapoptosis. Therefore, this study aimed to investigate whether 
      activated PPARbeta/delta could protect type 2 diabetic rats from lipoapoptosis through 
      regulation of GPR40 and to compare the protective effects of activated PPARbeta/delta 
      and PPARgamma. We made an animal model of type 2 diabetic lipoapoptosis by feeding 
      spontaneously type 2 diabetic Goto-Kakizaki (GK) rats with a high-fat diet (HFD) 
      to evaluate the effects of PPARbeta/delta on islet beta cell apoptosis. And, treated INS-1 
      cells with 0.5 mM palmitate (PAM) in the absence/presence of GW501516 (a specific 
      agonist of PPAR beta/delta) and with/without transfection of GPR40 siRNA to explore the 
      underlying molecular mechanism. HFD aggravated GK rats' poorer INSR30, lower 
      mass, greater apoptosis of beta cells, lower mass, and lower expression of GPR40, 
      which were similarly improved by GW501516 at 3 or 6 mg/kg day and pioglitazone. 
      Compared with pioglitazone, GW501516 caused more weight loss and had no effect on 
      insulin resistance. GW501516 protected INS-1 cells from PAM-induced apoptosis by 
      upregulating GPR40 and activating Akt/Bcl-2/caspase-3. Activated extracellular 
      regulated protein kinases (ERK) was relevant to the lipoapoptosis in INS-1 cells, 
      but was not involved in the antilipoapoptotic effect of GW501516. These results 
      showed that the PPARbeta/delta agonist GW501516 protected beta cells from lipoapoptosis and 
      improved beta cell mass by upregulating GPR40 and activating the Akt/Bcl-2/caspase-3 
      pathway, but not the ERK-signaling pathway.
CI  - (c) 2019 The Authors. Lipids published by Wiley Periodicals, Inc. on behalf of 
      American Oil Chemists' Society.
FAU - Li, Juan
AU  - Li J
AD  - Department of Endocrinology and Metabolism, West China Hospital of Sichuan 
      University, 37 Guoxuexiang, Chengdu, 610041, China.
FAU - Xu, Shishi
AU  - Xu S
AD  - Department of Endocrinology and Metabolism, West China Hospital of Sichuan 
      University, 37 Guoxuexiang, Chengdu, 610041, China.
FAU - Liu, Yuqi
AU  - Liu Y
AD  - Department of Endocrinology and Metabolism, West China Hospital of Sichuan 
      University, 37 Guoxuexiang, Chengdu, 610041, China.
FAU - Yan, Zhe
AU  - Yan Z
AD  - Department of Endocrinology and Metabolism, West China Hospital of Sichuan 
      University, 37 Guoxuexiang, Chengdu, 610041, China.
FAU - Zhang, Fang
AU  - Zhang F
AD  - Department of Endocrinology and Metabolism, West China Hospital of Sichuan 
      University, 37 Guoxuexiang, Chengdu, 610041, China.
FAU - Lv, Qingguo
AU  - Lv Q
AD  - Department of Endocrinology and Metabolism, West China Hospital of Sichuan 
      University, 37 Guoxuexiang, Chengdu, 610041, China.
FAU - Tong, Nanwei
AU  - Tong N
AD  - Department of Endocrinology and Metabolism, West China Hospital of Sichuan 
      University, 37 Guoxuexiang, Chengdu, 610041, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190730
PL  - United States
TA  - Lipids
JT  - Lipids
JID - 0060450
RN  - 0 (G-protein-coupled receptor 40, rat)
RN  - 0 (Lipids)
RN  - 0 (PPAR delta)
RN  - 0 (PPAR-beta)
RN  - 0 (Receptors, G-Protein-Coupled)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Diabetes Mellitus, Experimental/metabolism/pathology
MH  - Diabetes Mellitus, Type 2/*metabolism/pathology
MH  - Disease Models, Animal
MH  - Insulin-Secreting Cells/*cytology/*metabolism/pathology
MH  - Lipids/chemistry
MH  - Male
MH  - PPAR delta/*metabolism
MH  - PPAR-beta/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, G-Protein-Coupled/*metabolism
OTO - NOTNLM
OT  - GK rat
OT  - GPR40
OT  - Lipoapoptosis
OT  - PPARbeta/delta
OT  - Pancreatic beta-cell
EDAT- 2019/08/01 06:00
MHDA- 2020/05/14 06:00
CRDT- 2019/08/01 06:00
PHST- 2018/07/29 00:00 [received]
PHST- 2019/06/17 00:00 [revised]
PHST- 2019/07/08 00:00 [accepted]
PHST- 2019/08/01 06:00 [pubmed]
PHST- 2020/05/14 06:00 [medline]
PHST- 2019/08/01 06:00 [entrez]
AID - 10.1002/lipd.12182 [doi]
PST - ppublish
SO  - Lipids. 2019 Oct;54(10):603-616. doi: 10.1002/lipd.12182. Epub 2019 Jul 30.