Peroxisome proliferator activated receptor β agonist, GW501516,ameliorates insulin resistance in glucose intolerant mouse model
10.3867/j.issn.1000-3002.2008.02.002
- VernacularTitle:过氧化物酶体增殖物激活受体β亚型激动剂GW501516对胰岛素抵抗模型小鼠的胰岛素增敏作用
- Author:
Wei CHEN
;
Lili WANG
;
Hongying LIU
;
Jianlei KANG
;
Song LI
- Publication Type:Journal Article
- Keywords:
peroxisome proliferator-activated receptor β;
insulin resistance;
GW501516;
metabolic syndrome
- From:
Chinese Journal of Pharmacology and Toxicology
2008;22(2):88-94
- CountryChina
- Language:Chinese
-
Abstract:
AIM The effects of GW501516, a peroxisome proliferator-activated receptor β (PPARβ) agonist, in long term diet induced obesity (DIO, high fat and maltose diet for 4 months) mice were evaluated, and the efficacy of GW501516 against insulin resistance and the involved mechanism was investigated. METHODSMice were divided into 3 groups: normal control, DIO model and DIO model+GW501516. GW501516 (10 mg·kg-1·d-1) was administered by ig once a day for 14 d. During the treatment, body weight and food intake were monitored every other day. The oral glucose tolerance test, and the serum biochemical parameters including the serum triglyceride, total cholesterol and high density lipoprotein cholesterol (HDL-C) levels were measured according to the specifications. To confirm the GW501516-mediated PPARβ activation, the mRNA levels of downstream genes related to glucose, lipid metabolism and energy expenditure was measured. RESULTS GW501516 treatment effectively improved the glucose intolerance, increased the area under the glucose curves[DIO model, (32.4±4.6) mmol·h·L-1 compared with DIO model+GW501516, (23.4±2.5) mmol·h·L-1, n=7-8, P<0.05], normalized the fasted blood glucose, and increased serum HDL-C level, besides, histological analysis revealed the decreased hepatic lipid accumulation and hypertrophy of hepatocyte in DIO mice. Moreover, RT-PCR results indicated that carnitine palmitoyltransferase 1b, uncoupling protein 2, uncoupling protein 3 and glucose transport protein 4 were all upregulated. CONCLUSIONGW501516 significantly ameliorates glucose intolerance, decreases fasted blood glucose and hepatic steatosis, which might be related to ① the enhancement of fatty acid oxidation and energy uncoupling in muscle, and ②the improvement of insulin-stimulated glucose transportation in skeletal muscle in the long term DIO mice.
