胰岛素抵抗细胞模型的胰岛素降解酶活性与胰岛素敏感性的关系  

Relationship between insulin-degrading enzyme activity and insulin sensitivity in cell model of insulin-resistance

作　　者：李晨钟[1] 张素华[2] 舒昌达[2] 任伟[2] 

机构地区：[1]第一军医大学南方医院内分泌科,广东广州510515 [2]重庆医科大学附属第一医院内分泌科,重庆400016

出　　处：《第一军医大学学报》2002年第2期151-154,共4页Journal of First Military Medical University

基　　金：四川省卫生厅基金(920047);重庆市科委应用基础研究基金(97-4-175);广东省卫生厅基金(A2000378)

摘　　要：目的研究胰岛素降解酶(IDE)活性变化与胰岛素抵抗(IR)发生、发展之间的关系。方法以目前公认的IR细胞模型-高浓度胰岛素诱导培养的原代大鼠肝细胞为研究对象,检测细胞的IDE活性和反映细胞胰岛素敏感性的14C-2-脱氧葡萄糖掺入率及14C-醋酸盐掺入率,并观察IDE活性增强剂碘乙酰胺和IDE活性抑制剂氯喹对上述指标的影响。结果IR细胞模型IDE活性显著高于对照细胞,两种掺入率显著低于对照细胞,而且IR细胞模型IDE活性与两种掺入率呈显著负相关关系。此外,碘乙酰胺可显著提高IR细胞模型IDE活性,但显著降低其两种掺入率;氯喹的作用则与其刚好相反。结论IDE活性异常升高可能是引起大鼠肝细胞胰岛素敏感性下降的原因之一;胰岛素降解抑制剂氯喹可能通过抑制胰岛素降解过快所致的IR,从而改善机体的胰岛素敏感性。Objective To investigatetherelationshipbetweeninsulin-degradingenzyme(IDE)activityandtheonsetand developmentof insulinresistance(IR).Methods RatprimaryhepatocyteswithIRinducedby highconcentrationof human insulinwereusedin whichtheincorporationratesof14C-2-deoxyglucoseand14C-acetateweredeterminedto estimatethe insulinsensitivityof thecellsandIDEactivitywas assessed.Theeffectsof IDEinhibitor,chloroquine,andIDEactivator,iodoacetamide,on theseindiceswereobserved.Results IDEactivityof IRcellswas increased,and14C-2-deoxyglucoseand14C-acetateincorporationrateswere decreasedas comparedwiththe controlcells.Significantinversecorrelationwas observedbetweenIDEactivityof IRcellsandtheincorporationratesof14C-2-deoxyglucoseand14C-acetate.Iodoacetamide resultedin increasein IDEactivityand decreasein theincorporationrateswhilechloroquineactedto thereverseeffects.Conclusions IncreasedIDEactivitymay be one of themechanismsof IR genesisin ratprimaryhepatocytesculturedwith highconcentrationof IDE,chloroquine,on theotherhand,mayameliorateinsulinsensitivityby inhibitingacceleratedinsulin degradation.

关 键 词：胰岛素 抗药性 胰岛素溶酶 敏感性 

分 类 号：R587.1[医药卫生—内分泌]