Glucagon like peptide一1 protects human umbilical vein endothelial cells against endoplasmic reticulum stress and apoptosis induced by constant or fluctuating high glucose via regulating the expression level of glucose regulated proteins 78凡

Objective To investigate the effect and mechanism of glucagon like peptide-1(GLP-1) on endothelial cell endoplasmic reticulum stress (ER stress) and apoptosis induced by constant or fluctuating high glucose. Methods Cultured human umbilical vein endothelial cells (HUVECs) were divided into 6 groups: normal glucose control (cultured with 5.5 mmol/L glucose), constant high glucose (cultured with 30 mmol/L glucose), fluctuating high glucose (cultured with high glucose and normal glucose, changed every 12 hours), normal glucose control+10 nmol/L GLP-1, constant high glucose+10 nmol/L GLP-1, fluctuating high glucose+10 nmol/L GLP-1. The later 3 groups were pretreated with 10 nmol/L GLP-1 for 30 minutes, then cultured with corresponding glucose. After treatment for 48 h, the apoptosis rate of HUVECs was measured by flow cytometer, the glucose regulated proteins 78(GRP78) expression level was measured by Western blotting methods. HUVECS were treated by 30 mmol/L high glucose plus GLP-1 or not, then GRP78 expression level at different times (0, 3, 6, 12, 24, 48 h) was measured by using Western blotting methods. Differences between two groups were compared by LSD-t test, differences among more than two groups were compared by one-way analysis of variance. Results Assuming apoptosis rate of normal control group was 1, the apoptosis rate in fluctuating high glucose group was (1.2±0.05), which was significantly higher than that of control group(F=45.086, P 0.05). The GRP78 expression in constant high glucose group was 0.96±0.10, while it was 0.77±0.04 in fluctuating high glucose group(t=3.134, P<0.05). Conclusions Both constant and fluctuating high glucose can induce ER stress and apoptosis in HUVECS, the latter has stronger effect by further inhibition of GRP78 expression, GLP-1 can alleviate the ER stress and apoptosis by inducing the expression of GRP78. Key words: Glucagon like peptide-1; Fluctuating high glucose; Glucose regulated proteins 78; Human umbilical vein endothelial cells