[Summary] Type 2 diabetic patients often have risk factors such as hyperglycaemia ,dyslipidaemia , hypertension ,obesity and insulin resistance ,which increase the risks of vascular endothelial dysfunction and cardiovascular events. GLP-1 analogue and its receptor agonist ,is a novel therapy on diabetes targeting at incretin ,which can effectively control blood glucose and improve vascular endothelial dysfunction. Here we summarize the protective effect of GLP-1 analogue and its receptor agonist on vascular endothelial cell.

OBJECTIVETo investigate the protective effects of exendin-4 on vascular endothelial cells and explore the possible mechanism.

METHODSHuman umbilical vascular endothelial cells (HUVECs) were cultured in the presence of high glucose and tumor necrosis factor-α (TNF-α, 10 ng/ml) with or without exendin-4. The level of nitric oxide (NO) in the cell culture supernatant was measured using a nitrate reductase method. The expression of intercellular adhesion molecule-1 (ICAM-1) mRNA was measured by real-time PCR, and nuclear factor-κB (NF-κB) p65 translocation was detected using immunofluorescence assay. Western blotting was employed to measure the expression of p38 MAPK protein in the treated cells.

RESULTSIn the presence of high glucose and TNF-α, treatment of cells with exendin-4 did not obviously affect the cellular synthesis of NO, but significantly down-regulated the expression of ICAM-1 mRNA (P<0.01). The nuclear fluorescence intensity of NF-κB p65 and the expression level of p38 MAPK protein in the cells were significantly lowered by exendin-4 treatment (P<0.01).

CONCLUSIONExendin-4 ameliorates high glucose- and TNF-α-induced HUVEC-12 cell damage by inhibiting the expression of p38 MAPK protein and translocation of NF-κB p65.

Cell Line ; Culture Media ; chemistry ; Glucose ; adverse effects ; Human Umbilical Vein Endothelial Cells ; drug effects ; metabolism ; Humans ; Peptides ; pharmacology ; Transcription Factor RelA ; metabolism ; Tumor Necrosis Factor-alpha ; adverse effects ; Venoms ; pharmacology ; p38 Mitogen-Activated Protein Kinases ; metabolism