高脂饮食对小鼠胰岛功能及胰腺组织中TCF7L2/GLP-1的影响OACSTPCD
Effects of high-fat diet on islet function and TCF7L2/GLP-1 in pancreatic tissues of mice
目的 探讨高脂饮食对小鼠胰岛功能及胰腺组织中转录因子7-类似物2(TCF7L2)与胰高血糖素样肽-1(GLP-1)的影响.方法 30只小鼠随机均分为2组:正常对照组和高脂饮食(T2DM模型)组,分别连续24周喂养普通饲料和60％高脂饲料.连续喂养24周后比较两组小鼠的体质量以及胰岛功能等相关指标的差异;检测小鼠不同时间点的血糖水平,血浆中胰岛素、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、总胆固醇(TC)和甘油三酯(TG)的水平,胰腺组织中 TCF7L2、GLP-1和胰高血糖素样肽-1受体(GLP-1R)蛋白的表达水平和mRNA转录水平.结果 与正常对照组比较,高脂饮食组小鼠的体质量显著增加(P＜0.01),葡萄糖耐量和胰岛素耐受能力明显受损(P＜0.05),HDL-C、LDL-C、TC、TG、空腹血糖和胰岛素的水平明显增加(P＜0.05),而TCF7L2、GLP-1和GLP-1R的mRNA和蛋白表达水平明显降低(P＜0.01).另外,与正常对照组相比,高脂饮食组小鼠胰腺组织的胰岛形态不规则,体积增大,血管数量增多,扩张充血显著.结论 高脂饮食的T2DM小鼠,胰腺组织胰岛形态改变,胰岛功能降低,TCF7L2表达水平降低,并且GLP-1和GLP-1R表达水平同步降低.
Objective To investigate the effects of high fat diet(HFD)on islet function and the expressions of transcription factor 7-analogue 2(TCF7L2)and glucagon-like peptide-1(GLP-1)in pancreatic tissue of mice.Methods Thirty mice were randomized into two groups:normal control(NC)group and HFD group,and the mice in two groups were fed with ordinary diet or 60％high fat diet to induce the type 2 diabetes mellitus(T2DM)model,respectively.After continuous feeding for 24 weeks,the differences in body weight,islet function and other related indicators were compared between two groups.The blood glucose levels of mice were detected by glucose tolerance test,insulin tolerance test and fasting blood glucose test at different time points.The levels of insulin,GLP-1,high density lipoprotein(HDL-C),low density lipoprotein(LDL-C),total cholesterol(TC)and triglyceride(TG)in plasma of mice were detected by ELISA kit.The protein levels of TCF7L2,GLP-1 and glucagon-like peptide-1 receptor(GLP-1 R)in pancreatic tissues of mice were detected by immunohistochemistry and Western blot.The mRNA levels of TCF7L2,GLP-1 and GLP-1 R were tested by quantitative real time polymerase chain reaction assay.Results Compared with NC group,the body weight was significantly increased in HFD group(P＜0.01),and the glucose tolerance and the insulin tolerance of mice were significantly impaired(P＜0.05).Compared with NC group,the contents of fasting HDL-C,LDL-C,TC,TG,blood glucose,and insulin were significantly upregulated in HFD group(P＜0.05).The mRNA and protein expression levels of TCF7L2,GLP-1 and GLP-1 R in HFD group were significantly decreased compared to NC group(P＜0.01).Moreover,compared with NC group,the pancreatic islets of mice in HFD group were irregular in shape,enlarged in size,and the blood vessels were increased in the number,and significantly dilated and congested.Conclusion In high-fat T2DM mice,the morphology of pancreatic islet changes,the islet function decreases,TCF7L2 expression level decreases,and GLP-1 and GLP-1 R expression levels decrease simultaneously.
孟齐;艾比拜·玉素甫;刘华;蒋升
省部共建中亚高发病成因与防治国家重点实验室,新疆医科大学第一附属医院内分泌科,乌鲁木齐 830000
临床医学
2型糖尿病转录因子7类似物2胰高血糖素样肽-1胰腺胰岛素
type 2 diabetes mellitusTCF7L2GLP-1pancreasinsulin
《山西医科大学学报》 2024 (007)
872-878 / 7
新疆维吾尔自治区科技创新团队(天山创新团队)项目(2022TSCXTD0014)
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