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

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.