title: Effect of Glucagon-like Peptide-1 on High-Glucose-induced Oxidative Stress and Cell Apoptosis in Human Endothelial Cells and Its Underlying Mechanism.
abstract: Glucagon-like peptide-1 (GLP-1) has been demonstrated to play an important role in type 2 diabetes mellitus, leading to cardiovascular diseases. This study aimed to examine the GLP-1 regulation of high-glucose-induced oxidative stress and cell apoptosis in human umbilical vein endothelial cells (HUVECs) and its underlying mechanism. HUVECs were isolated from healthy umbilical cords and cultured. GLP-1 and the GLP-1R antagonist, exendin (9-39), were used to pretreat the cells. The expression of NADPH oxidase subunits gp91 and p22 messenger RNA was detected by real-time quantitative polymerase chain reaction. Reactive oxygen species production was detected with flow cytometry and fluorescence microscopy. Lucigenin assay was used to measure the NADPH oxidase activity. The terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assay was used to investigate endothelial cell apoptosis. Apoptosis proteins were detected by immunoblotting. GLP-1 decreased high-glucose-induced oxidative stress, the expression of gp91 and p22phox messenger RNAs, and NADPH oxidase activation. Exendin (9-39) antagonized the effects of GLP-1 on high-glucose-induced oxidative stress. GLP-1 also increased HUVEC's high-glucose-induced proliferation and inhibited apoptosis. GLP-1 inhibited high-glucose-induced oxidative stress and cell apoptosis in HUVECs through GLP-1R-dependent and GLP-1 (9-36)-related pathways. GLP-1 suppressed high-glucose-induced oxidative stress and consequently may have an antiatherosclerosis effect on diabetes mellitus patients.
authors: *Department of Cardiology, Zhujiang Hospital of Southern Medical University, Guangzhou, China; and †Department of Cardiology, Fujian Provincial Hospital, Fuzhou, China.
authors: Rehua
authors: R
authors: Wang
authors: Lihong
authors: L
authors: Lu
authors: Yansong
authors: Y
authors: Guo
authors: Feng
authors: F
authors: Lin
authors: Haifeng
authors: H
authors: Chen
authors: Wei
authors: W
authors: Chen
authors: Minsheng
authors: M
authors: Chen
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D005947:Glucose / Q000008:administration & dosage / Q000633:toxicity*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D052216:Glucagon-Like Peptide 1; D005947:Glucose