期刊
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
卷 18, 期 4, 页码 333-339出版社
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
DOI: 10.4196/kjpp.2014.18.4.333
关键词
Exendin-4; Glucose transporter 4; Nonalcoholic fatty liver disease; ob/ob
资金
- Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [A111436]
- Korea Health Promotion Institute [A111436] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor (GLP-1R) agonist, has been known to reverse hepatic steatosis in ob/ob mice. Although many studies have evaluated molecular targets of Ex-4, its mechanism of action on hepatic steatosis and fibrosis has not fully been determined. In the liver, glucose transporter 4 (GLUT4) is mainly expressed in hepatocytes, endothelial cells and hepatic stellate cells (HSCs). In the present study, the effects of Ex-4 on GLUT4 expression were determined in the liver of ob/ob mice. Ob/ob mice were treated with Ex-4 for 10 weeks. Serum metabolic parameters, hepatic triglyceride levels, and liver tissues were evaluated for hepatic steatosis. The weights of the whole body and liver in ob/ob mice were reduced by long-term Ex-4 treatment. Serum metabolic parameters, hepatic steatosis, and hepatic fibrosis in ob/ob mice were reduced by Ex-4. Particularly, Ex-4 improved hepatic steatosis by enhancing GLUT4 via GLP-1R activation in ob/ob mice. Ex-4 treatment also inhibited hepatic fibrosis by decreasing expression of connective tissue growth factor in HSCs of ob/ob mice. Our data suggest that GLP-1 agonists exert a protective effect on hepatic steatosis and fibrosis in obesity and type 2 diabetes.
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