VEGFB调控胰岛素介导的胰高血糖素分泌抑制作用及其机制研究  

Mechanism of VEGFB on regulating insulin-mediated glucagon secretion inhibition

作　　者：张金涛 孟琴语 李文浩 许诺 朱子明 李雅娜 ZHANG Jintao;MENG Qinyu;LI Wenhao;XU Nuo;ZHU Ziming;LI Yanuo(Department of Pathophysiology,School of Basic Medical Sciences,Binzhou Medical University,Yantai 264003,Shandong,P.R.China;Department of Critical Care Medicine,Second School of Clinical Medicine,Binzhou Medical University,Yantai 264100,Shandong,P.R.China)

机构地区：[1]滨州医学院基础医学院病理生理学教研室,山东烟台264003 [2]滨州医学院第二临床医学院重症医学科,山东烟台264100

出　　处：《滨州医学院学报》2024年第6期459-464,共6页Journal of Binzhou Medical University

摘　　要：目的探讨血管内皮生长因子B(vascular endothelial growth factor B,VEGFB)通过作用于血管内皮生长因子受体1(vascular endothelial growth factor receptor 1,VEGFR1)对胰岛素介导的胰高血糖素分泌调节的抑制作用及其机制,为预防和治疗葡萄糖调节受损(impaired glucose regulation,IGR)提供可借鉴的理论和实验依据。方法通过高脂饮食喂养构建IGR模型小鼠,利用腺相关病毒感染IGR小鼠,分别观察VEGFB对标准饮食的C57BL/6小鼠(Chow组)、胰腺特异性VEGFB过表达小鼠(AAV-VEGFB组)和对照组小鼠(AAV-null组)生长状态、血糖水平、葡萄糖耐量、胰岛素敏感性、胰岛素及胰高血糖素的影响。通过蛋白免疫印迹技术(Western blot)验证VEGFB、VEGFR1蛋白表达水平,通过实时荧光定量聚合酶链反应技术(qRT-PCR)测定磷酸烯醇式丙酮酸羧激酶(PEPCK)和葡萄糖-6磷酸酶(G6Pase)的mRNA表达水平。结果VEGFB过表达后,AAV-VEGFB组小鼠的生长状态良好,其空腹血糖(FBG)、餐后血糖(PBG)及糖化血红蛋白(GHb)水平降低,葡萄糖耐量和胰岛素敏感性下降;胰岛素分泌水平上升,胰高血糖素的分泌量减少。结论VEGFB结合VEGFR1增加胰岛素分泌、降低胰高血糖素分泌,进而改善IGR小鼠的糖代谢平衡。Objective To investigate the inhibitory effect and mechanism of vascular endothelial growth factor B(VEGFB)on insulin-mediated pancreatic glucagon secretion regulation by acting on vascular endothelial growth factor receptor 1(VEGFR1),and to provide theoretical and experimental basis for the prevention and treatment of impaired glucose regulation(IGR).Methods By infecting IGR mice with adenovirus,we observed the effects of VEGFB on the growth status,blood glucose levels,insulin,glucagon,and pancreatic morphology of C57BL/6 mice fed a standard diet(Chow group),mice overexpressing pancreatic-specific VEGFB(AAV-VEGFB group),and control mice(AAV-null group).VEGFB and VEGFR1 protein expression levels were verified using Western blotting,and mRNA expression levels of glucose metabolism genes phosphoenolpyruvate carboxykinase(PEPCK)and glucose-6-phosphatase(G6Pase)were determined by using quantitative polymerase chain reaction(qPCR)technique.Results After VEGFB overexpression,mice in the AAV-VEGFB group exhibited good growth status,with decreased fasting blood glucose(FBG),postprandial blood glucose(PBG),and glycated hemoglobin(GHb)levels,along with reduced glucose tolerance and insulin sensitivity.The level of insulin secretion increased,and the amount of glucagon secretion decreased.Conclusion VEGFB combined with VEGFR1 increased insulin secretion and decreased glucagon secretion,thereby improving the glucose metabolism balance of IGR mice.

关 键 词：血管内皮生长因子B 血管内皮生长因子受体1 胰岛素 胰高血糖素 葡萄糖调节受损 

分 类 号：R363[医药卫生—病理学]