摘要
目的:观察血浆游离脂肪酸(FFA)水平升高对β细胞胰岛素分泌功能的影响,探讨β细胞胰岛素信号通路在其中所起的作用及其机制。方法:将8周龄雄性SD大鼠随机分为脂肪乳输注组(FFA组,13只)和生理盐水输注组(NS组,12只)。分别输注48h,检测以下指标:(1)采血检测胰岛素,FFA水平;(2)正常血糖高胰岛素钳夹实验,评价外周组织胰岛素抵抗程度;(3)静脉葡萄糖耐量实验,评价活体胰岛β细胞分泌功能;(4)胰岛细胞表面灌注实验,评价离体胰岛β细胞动态分泌功能;(5)采用实时荧光定量PCR方法检测肌肉中胰岛素受体底物-1(IRS-1)、胰岛素受体底物-2(IRS-2)mRNA表达的变化;(6)用实时荧光定量PCR方法检测胰岛细胞IRS-1,IRS-2和葡萄糖转运子-2(Glut-2)mRNA表达的变化。结果:(1)FFA组血中胰岛素水平比NS组增高[(24.44±1.25)mIU/Lvs(18.09±1.37)mIU/L,P<0.05],FFA水平也显著高于NS组[(1.39±0.18)mmol/Lvs(0.64±0.10)mmol/L,P<0.001];(2)FFA刺激后,离体和活体的胰岛β细胞分泌功能均增强;(3)FFA组葡萄糖输注率(GIR)较NS组明显降低(P<0.05),提示存在明显的外周胰岛素抵抗;(4)FFA组肌肉IRS-1mRNA表达比NS组降低87.7%,IRS-2表达降低50.7%(P<0.05);(5)FFA组胰岛细胞IRS-1mRNA表达增加29.3%(P<0.05),IRS-2及Glut-2分别增加345.1%和536.4%(P<0.01)。结论:血浆FFA水平短期升高,造成外周胰岛素抵抗的同时,对β细胞胰岛素分泌有刺激作用,此时胰岛细胞胰岛素信号通路分子基因表达增加。
Objective：To study the changes and mechanism of the function of islet β cells and insulin signal transduction molecules after lipid infusion.Methods：Twenty five SD rats were randomly divided into 2 groups,FFA group and NS group.Catheters were implanted under pentobarbital anesthesia in the right atrium via the jugular vein and the left carotid artery.A technique for a 48 h infusion in unrestrained rats was used for triglyceride and heparin or saline infusion.The infusion period started on day 2 after surgery.After 48 h infusion,we determined fasting serum insulin（Ins）,free fat acid（FFA）in the blood.The glucose infusion rate（GIR）was measured by hyperinsulinemia euglycemic clamp to evaluate the perpherial insulin resistance.The ivgtt and islet cell perifusion was conducted to evaluate the function of islet β cells.The rats in the two groups were sacrificed,and the pancreatic islets were isolated and collected.The expressions of insulin receptor substrate-1（IRS-1）,insulin receptor substrate-2（IRS-2）glucose transporter-2（Glut-2）gene in islets and IRS-1,IRS-2 in muscle were detected by real-time PCR.Results（1）The serum FFA and insulin concentrations of blood in FFA group were higher than in NS group（P〈0.05）.（2）The GIR was decreased significantly in FFA group compared with that in NS group（P〈0.05）.（3）The glucose stimulated insulin secretion increased in the FFA group.（4）The gene expression of IRS-1 in muscle was significantly decreased by 87.7% in FFA group,and the expression of IRS-2 was decreased by 50.7%（all P〈0.05）.The gene expression of IRS-1 in islets was significantly increased by 29.3%（P〈0.05）,and the expressions of IRS-2,Glut-2 were increased by 345.1% and 536.4% respectively,in FFA group（all P〈0.01）.Conclusion：Lipid infusion in short time increased the secretion of insulin and impaired expression of insulin signal transduction molecules in muscle but it also increased the expression of insulin signal transduction molecules in islet β cells.
出处
《北京大学学报（医学版）》
CAS
CSCD
北大核心
2007年第5期462-466,共5页
Journal of Peking University:Health Sciences
基金
国家自然科学基金资助项目(30640081)~~
关键词
胰岛素抗药性
脂肪酸类
非酯化
聚合酶链反应
Insulin resistance
Fatty acids,nonesterified
Polymerase chain reaction
