王平 1郭晓宇 1高宇 2刘剑 1山秀杰 2张蕊 2葛晓春 2冯增斌 2李桂芳2
作者信息
- 1. 承德医学院,河北承德067000
- 2. 承德医学院附属医院内分泌科 067000
- 折叠
摘要
Abstract
Objective To observe the effects of liraglutide on GRP78,ATF4,CHOP and TRB3 protein and mRNA expression in rats which fed with high fat diet,and to explore the effect of liraglutide on ATF4/CHOP pathway of pancreas in rats fed with high fat diets.Methods Forty-four male Wistar rats were randomly divided into the control group,high fat group,intervention group 1 and intervention group 2,11 cases in each group.The control group was fed with common food,other 3 groups were fed with high fat diet for 8 weeks.Then the intervention group 1 was given with liraglutide (100 μg · kg-1 · d-1) by subcutaneous injection;the intervention group 2 was given liraglutide (200 μg · kg-1 · d-1) by subcutaneous injection.After 2 weeks medication intervention,the rats were killed.Five rats were taken from each group and performed the hyperinsulinemic englycemic clamp experiment under waking state for calculating the glucose infusion rate (GIR).The fasting blood glucose (FBG),fasting insulin (FINS),serum free fatty acid (FFA),total cholesterol (TC),triglyeeride (TG),low density lipoprotein cholesterol (LDL-C) and high density lipoprotein(HDL) were examined,and islet beta cell function index(HOMA-β) were calculated.PCR and Western blot method were used to detect the expression of pancreas GRP78,ATF4,CHOP and TRB3 protein and mRNA.Results Compared with the control group,the levels of FBG,FFA,TC,FINS,TG and LDL-C in the high fat group were significantly increased,the levels of HDL-C,GIR and HOMA-β were significantly decreased(P＜0.05 or P＜0.01);compared with the high fat group,the levels of HDL-C,GIR and HOMA-β in the intervention group 2 were increased(P＜0.05 or P＜0.01),the other indicators were significantly decreased;compared with the intervention group 1,blood FGB,FFA,TC in the intervention group 2 were decreased,while the levels of GIR and HOMA-β were increased(P＜0.05).Compared with the control group,expression of GRP78,ATF4,CHOP and TRB3 protein and mRNA in the high fat group were significantly increased;compared with the high fat group,the expression of GRP78,ATF4,CHOP and TRB3 protein and mRNA in the intervention group 1 and 2 were gradually decreased with the liraglutide concentration increase.Conclusion Liraglutide can improve insulin resistance and protect pancreatic beta cells in a concentration-dependent manner,its mechanisms may involve in the pancreatic endoplasmic reticulum ATF4/CHOP pathway.关键词
胰岛素抗药性/内质网应激/转录活化因子-4/CCAAT/增强子结合蛋白同源蛋白/利拉鲁肽Key words
insulin resistance/endoplasmic reticulum stress/ATF4/CCAAT/EBP homologous protein/liraglutide分类
医药卫生
