Activated PPARβ/δ Protects Pancreatic β Cells in Type 2 Diabetic Goto-Kakizaki Rats from Lipoapoptosis via GPR40

被引：0
作者：
Li, Juan [1 ]
Xu, Shishi [1 ]
Liu, Yuqi [1 ]
Yan, Zhe [1 ]
Zhang, Fang [1 ]
Lv, Qingguo [1 ]
Tong, Nanwei [1 ]
机构：
[1] Sichuan Univ, West China Hosp, Dept Endocrinol & Metab, 37 Guoxuexiang, Chengdu 610041, Sichuan, Peoples R China
来源：
LIPIDS | 2019年 / 54卷 / 10期
基金：
中国国家自然科学基金;
关键词：
GK rat; GPR40; Lipoapoptosis; Pancreatic beta-cell; PPAR beta; delta; INDUCED OXIDATIVE STRESS; INSULIN SENSITIVITY; EXPRESSION; GLUCOSE; DELTA; APOPTOSIS; SECRETION; MODEL; BASAL;
D O I：
10.1002/lipd.12182ORIGINAL
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 PPAR beta/delta could protect type 2 diabetic rats from lipoapoptosis through regulation of GPR40 and to compare the protective effects of activated PPAR beta/delta and PPAR gamma. 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 PPAR beta/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 PPAR beta/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.
引用
收藏
页码：603 / 616
页数：14
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