Author + information
- 1Department of medicine, Hubei University of Science and Technology, Xianning, China
- 2Department of pharmacology, Hubei University of Science and Technology, Xianning, China
- 3Department of cardiovascular medicine, Xianning Central Hospital, The First Affiliated Hospital Of Hubei University Of Science And Technology, Jingu
Diabetes mellitus is a prominent risk factor for cardiovascular diseases. Diabetic cardiomyopathy is an important complication of the heart independent of hypertension and coronary artery disease and is accompanied by cardiomyopathy. The underlying mechanisms for the development of diabetic cardiomyopathy (DCM) are complex and not completely understood. Glucagon-like peptide 1 (GLP-1) is an incretin hormone, accumulating evidence has implicated that GLP-1 may have a beneficial effect on cardiovascular but the mechanism is not fully understood. The purpose of this study was to investigate whether GLP-1 analog, liraglutide, exerts the therapeutic effect on streptozotocin-induced DCM in rats.
Type 2 diabetic rats were sacrificed after administration withTSG for 8 weeks. Blood glucose, blood lipids, liver function, creatine kinase (CK), lactate dehydrogenase (LDH) as well as myocardial nonesterified fatty acids (NEFA) were determined by usingbiochemical test. The concentration of myocardial fatty acid transport proteins(FATPs) andfatty acidβ-oxidase (FA-β-oxidase),and the levels of tumor necrosis factor alpha(TNF-α), interleukin -6 (IL-6), interleukin-1β(IL-1β)in serum were also measured by ELISA method. The mRNA expressions of NADPH oxidase isoforms p67phox, p22phox, and p91phoxwere detected by qPCR. The protein expressions of c-Jun NH2-terminal kinase (JNK), P38, and NF-κB were detected by Westernblot.
Treatment of liraglutide reduced the content of blood lipids, NEFA and collagen without effecting the content of blood glucose and insulin. Treatment of liraglutide caused a significant increased concentration of myocaidial FATPs and FA-β-oxidase. The levels of TNF-α, IL-6 and IL-1βin serum were inhibited by administration with liraglutide. Liraglutide treatment also blunted the mRNA expression of NADPH oxidase isoforms p67phox, p22phox, and p91phox, and abated oxidative stress. Liraglutide inhibited the activation of c-Jun NH2-terminal kinase (JNK), P38, and NF-κB in the cardiac tissue of diabetic rats.
These findings indicate that the protective mechanisms of GLP-1 analog, liraglutide against diabetic rats are involved in the alleviation of inflammatory mediators injury, oxidative stress and suppression of JNK, P38, and NF-κB signaling pathways.
Key words: GLP-1; Diabetic cardiomyopathy; NADPH oxidase; liraglutide; JNK [Acknowledgements] This work was supported by the Foundation from Department of Education of Hubei Province (D20162803), Health and Family Planning Commission of Hubei Province(WJ2015Z122) and the Foundation from Hubei University of Science and Technology(LCZX201515).