Glucagon-like peptide-1 (GLP-1) protects vascular endothelial cells against advanced glycation end products (AGEs) – induced apoptosis
Yi Zhan, Hui-lin Sun, Hong Chen, Hua Zhang, Jia Sun, Zhen Zhang, De-hong Cai
Med Sci Monit 2012; 18(7): BR286-291
Available online: 2012-06-28
Background: The peptide glucagon-like peptide-1 (GLP-1) is a hormone secreted by intestinal L cells in response to food intake. GLP-1 has been proposed as the basis of emerging therapy for patients with type 2 diabetes. However, the effects of GLP-1 on vascular injury in diabetes have not been identified. Advanced glycation end products (AGEs) induce endothelial cell apoptosis and have been implicated in the process of vascular complications from diabetes.
Material/Methods: The aim of this work was to investigate whether and how GLP-1 protects endothelial cells from apoptosis induced by AGEs. Human umbilical vein endothelial cells (HUVECs) were treated with AGEs (200 µg/mL) for 48 h in the presence or absence of GLP-1. Cell morphology, viability, apoptosis, ratio of Bcl-2 protein to Bax protein, cytochrome c release, and activity of caspase-9 and -3 were determined.
Results: Treatment of cells with AGEs led to cell morphology changes and decreased cell viability, resulting in apoptosis. GLP-1 alone increased cell viability in a concentration-dependent manner. GLP-1 partially inhibited AGEs-induced apoptosis in HUVECs. GLP-1 increased Bcl-2/Bax ratio, reduced cytochrome c levels in the cytoplasm, and reduced the activity of caspase-9 and -3 in AGEs-treated HUVECs.
Conclusions: AGEs induces apoptosis via the mitochondrion-cytochrome c-caspase protease pathway, and GLP-1 protects endothelial cells by interfering with this mechanism. GLP-1 may represent an anti-apoptotic agent in the treatment of vascular complications arising from diabetes.
Keywords: Human Umbilical Vein Endothelial Cells - enzymology, Glycosylation End Products, Advanced - toxicity, Glucagon-Like Peptide 1 - pharmacology, Enzyme Activation - drug effects, Cytoprotection - drug effects, Cytochromes c - metabolism, Cell Survival - drug effects, Caspase 9 - metabolism, Caspase 3 - metabolism, Apoptosis - drug effects, Up-Regulation - genetics, bcl-2-Associated X Protein - metabolism