RasGAP-Derived Fragment N Increases the Resistance of Beta Cells towards Apoptosis in NOD Mice and Delays the Progression from Mild to Overt Diabetes 英文参考文献.docVIP

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RasGAP-Derived Fragment N Increases the Resistance of Beta Cells towards Apoptosis in NOD Mice and Delays the Progression from Mild to Overt Diabetes 英文参考文献.doc

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RasGAP-Derived Fragment N Increases the Resistance of Beta Cells towards Apoptosis in NOD Mice and Delays the Progression from Mild to Overt Diabetes 英文参考文献

RasGAP-DerivedFragmentNIncreasestheResistanceof BetaCellstowardsApoptosisinNODMiceandDelays theProgressionfromMildtoOvertDiabetes NatasaBulat,EvrimJaccard,NievesPeltzer,HadiKhalil,Jiang-YanYang,GillesDubuis,Christian Widmann* DepartmentofPhysiology,BiologyandMedicineFaculty,UniversityofLausanne,Lausanne,Switzerland Abstract Thecaspase-3-generatedRasGAPN-terminalfragment(fragmentN)inhibitsapoptosisinaRas-PI3K-Akt-dependentmanner. Fragment N protects various cell types, including insulin-secreting cells, against different types of stresses. Whether fragmentNexertsaprotectiveroleduringthedevelopmentoftype1diabetesishowevernotknown.Non-obesediabetic (NOD)micerepresentawell-knownmodelforspontaneousdevelopmentoftype1diabetesthatsharessimilaritieswiththe diseasesencounteredinhumans.ToassesstheroleoffragmentNintype1diabetesdevelopment,atransgeneencoding fragmentN underthecontrol oftheratinsulinpromoter(RIP) wasback-crossed intotheNODbackground creating the NOD-RIPNstrain.DespiteamosaicexpressionoffragmentNinthebetacellpopulationofNOD-RIPNmice,isletsisolated fromthesemiceweremoreresistanttoapoptosisthancontrolNODislets.Isletlymphocyticinfiltrationandoccurrenceofa mildincreaseinglycemiadevelopedwiththesamekineticsinbothstrains.However,theperiodoftimeseparatingthemild increase in glycemia and overt diabetes was significantly longer in NOD-RIPN mice compared to the control NOD mice. Therewasalsoasignificantdecreaseinthenumberofapoptoticbetacellsinsituat16weeksofageintheNOD-RIPNmice. Fragment N exerts therefore a protective effect on beta cells within the pro-diabetogenic NOD background and this preventsafastprogressionfrommildtoovertdiabetes. Citation:BulatN,JaccardE,PeltzerN,KhalilH,YangJ-Y,etal.(2011)RasGAP-DerivedFragmentNIncreasestheResistanceofBetaCellstowardsApoptosisin NODMiceandDelaystheProgressionfromMildtoOvertDiabetes.PLoSONE6(7):e22609.doi:10.1371/journal.pone.0022609 Editor:JanineSantos,UniversityofMedicineandDentistryofNewJersey,UnitedStatesofAmerica Receiv