Effects of glucagon-like peptide-1 on advanced glycation endproduct-induced aortic endothelial dysfunction in streptozot
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ORIGINAL ARTICLE
Effects of glucagon-like peptide-1 on advanced glycation endproduct-induced aortic endothelial dysfunction in streptozotocin-induced diabetic rats: possible roles of Rho kinase- and AMP kinase-mediated nuclear factor jB signaling pathways Song-tao Tang1,2,3 • Qiu Zhang3 • Hai-qin Tang4 • Chang-jiang Wang3 Huan Su2 • Qing Zhou2 • Wei Wei1 • Hua-qing Zhu2 • Yuan Wang1,2
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Received: 18 July 2015 / Accepted: 28 December 2015 Ó Springer Science+Business Media New York 2016
Abstract Interaction between advanced glycation endproducts (AGEs) and receptor for AGEs (RAGE) as well as downstream pathways leads to vascular endothelial dysfunction in diabetes. Glucagon-like peptide-1 (GLP-1) has been reported to attenuate endothelial dysfunction in the models of atherosclerosis. However, whether GLP-1 exerts protective effects on aortic endothelium in diabetic animal model and the underlying mechanisms are still not well defined. Experimental diabetes was induced through administration with combination of high-fat diet and intraperitoneal injection of streptozotocin. Rats were randomly divided into four groups, including controls, diabetes, diabetes ? sitagliptin (30 mg/kg/day), diabetes ? exenatide (3 lg/kg/12 h). Eventually, endothelial damage, markers of inflammation and oxidative stress, were measured. After 12 weeks administration, diabetic rats received Song-tao Tang is the first author.
Electronic supplementary material The online version of this article (doi:10.1007/s12020-015-0852-y) contains supplementary material, which is available to authorized users. & Hua-qing Zhu [email protected] & Yuan Wang [email protected] 1
Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China
2
Laboratory of Molecular Biology, Department of Biochemistry, Anhui Medical University, 81 Meishan Road, Hefei Zip code: 230032, Anhui Province, China
3
Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
4
Department of Geriatrics, The First Affiliated Hospital of Anhui Medical University, Hefei, China
sitagliptin and exenatide showed significant elevation of serum NO level and reduction of ET-1 as well as inflammatory cytokines levels. Moreover, sitagliptin and exenatide significantly inhibited aortic oxidative stress level and improved aortic endothelial function in diabetic rats. Importantly, these drugs inhibited the protein expression level in AGE/RAGE-induced RhoA/ROCK/NF-jB/IjBa signaling pathways and activated AMPK in diabetic aorta. Finally, the target proteins of p-eNOS, iNOS, and ET-1, which reflect endothelial function, were also changed by these drugs. Our present study indicates that sitagliptin and exenatide administrations can improve endothelial function in diabetic aorta. Of note, RAGE/RhoA/ROCK and AMPK mediated NF-jB signaling pathways may be the intervention targets of these drugs to protect aortic endothelium. Keywords Glucagon-like peptide-1 Advanced glycation endproducts Endothelial function Nuclear factor jB
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