title: Glucagon-like peptide 1 protects microvascular endothelial cells by inactivating the PARP-1/iNOS/NO pathway.
abstract: Increasing studies suggest that the activity of GLP-1 might be of significant importance in the development of type 2 diabetes beyond its serum glucose-lowering effects. However, to date, the anti-apoptosis mechanism by which GLP-1 acts on MILE SVEN 1 (MS-1) cells has not been fully explored with regard to the intracellular signaling pathway. Increasing evidence shows that apoptosis of islet microvascular endothelial cells (IMECs) participates in the pathogenesis of diabetes. We wondered whether GLP-1 exerts its anti-apoptosis effects by inactivating the PARP-1/iNOS/NO pathway in oxidized low-density-lipoprotein (oxLDL)-induced apoptosis in mouse IMECs (MS-1 cells), which may linked to GLP-1R/cAMP levels. MTT assay revealed that 2-h pre-incubation with GLP-1 markedly restored the oxLDL-induced loss of MS-1 viability in a concentration-dependent manner. This effect was accompanied by a significant decrease in intracellular nitric oxide (NO) activity. Moreover, GLP-1 suppressed lipid peroxidation, restored the activities of endogenous antioxidants, and decreased the level of NO. Pre-incubating MS-1 cells with GLP-1 reduced cell apoptosis. Finally, GLP-1 could efficiently prevent the upregulation of poly(ADP-ribose) polymerase-1/nitrotyrosine and inducible NO synthase protein. Simultaneously, the expression of GLP-1 receptor and the level of cAMP was consistent with the administration of GLP-1. Our findings suggest that GLP-1 can effectively protect MS-1 cells against oxLDL-induced apoptosis, which may be important in preventing the pathogenesis of diabetes mellitus.
authors: Department of Endocrinology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors: Fu-qiang
authors: FQ
authors: Liu
authors: Xiang-li
authors: XL
authors: Zhang
authors: Lei
authors: L
authors: Gong
authors: Xu-ping
authors: XP
authors: Wang
authors: Juan
authors: J
authors: Wang
authors: Xin-guo
authors: XG
authors: Hou
authors: Yu
authors: Y
authors: Sun
authors: Wei-dong
authors: WD
authors: Qin
authors: Shu-jian
authors: SJ
authors: Wei
authors: Yun
authors: Y
authors: Zhang
authors: Li
authors: L
authors: Chen
authors: Ming-Xiang
authors: MX
authors: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology*; D015870:Gene Expression / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology; D051379:Mice; D055806:Microvessels / Q000166:cytology*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D008077:Lipoproteins, LDL; D011994:Recombinant Proteins; C099252:oxidized low density lipoprotein; D009569:Nitric Oxide; D052216:Glucagon-Like Peptide 1; D000242:Cyclic AMP; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases