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12.01.2016 | Original Article | Ausgabe 1/2016

Endocrine 1/2016

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 κB signaling pathways

Zeitschrift:
Endocrine > Ausgabe 1/2016
Autoren:
Song-tao Tang, Qiu Zhang, Hai-qin Tang, Chang-jiang Wang, Huan Su, Qing Zhou, Wei Wei, Hua-qing Zhu, Yuan Wang
Wichtige Hinweise

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.
Song-tao Tang is the first author.

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 μg/kg/12 h). Eventually, endothelial damage, markers of inflammation and oxidative stress, were measured. After 12 weeks administration, diabetic rats received 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-κB/IκBα 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-κB signaling pathways may be the intervention targets of these drugs to protect aortic endothelium.

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Zusatzmaterial
Supplementary material 1 IPGTT and IPITT after HF diet treatment for 8 weeks. A and C. Serum glucose levels during IPGTT in HF rats were higher than those in controls. B and D. Serum glucose levels during IPITT in HF rats were higher than those in controls. Data are expressed as mean ± S.D. *P < 0.05 versus control group. 1. Control group (n = 7), 2. HF group (n = 18). HF: high-fat; IPGTT: intraperitoneal glucose tolerance test; IPITT: intraperitoneal insulin tolerance test; AUC: area under the curve; S.D: standard deviation. (TIFF 2527 kb)
12020_2015_852_MOESM1_ESM.tif
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