Postnatal Development of Numbers and Mean Sizes of Pancreatic Islets and Beta-Cells in Healthy Mice and GIPRdn Transgenic Diabetic Mice 英文参考文献.docVIP

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Postnatal Development of Numbers and Mean Sizes of Pancreatic Islets and Beta-Cells in Healthy Mice and GIPRdn Transgenic Diabetic Mice 英文参考文献.doc

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Postnatal Development of Numbers and Mean Sizes of Pancreatic Islets and Beta-Cells in Healthy Mice and GIPRdn Transgenic Diabetic Mice 英文参考文献

PostnatalDevelopmentofNumbersandMeanSizesof PancreaticIsletsandBeta-CellsinHealthyMiceand GIPRdn TransgenicDiabeticMice NadjaHerbach1*,MartinaBergmayr1,BurkhardGo¨ke2,EckhardWolf3,RuedigerWanke1 1InstituteofVeterinaryPathology,CenterforClinicalVeterinaryMedicine,LMUMunich,Germany,2DepartmentofInternalMedicineII,UniversityClinicGrosshadern, LMUMunich,Germany,3ChairforMolecularAnimalBreedingandBiotechnology,andLaboratoryforFunctionalGenomeAnalysis(LAFUGA),GeneCenter,LMUMunich, Germany Abstract The aim of this study was to examine postnatal islet and beta-cell expansion in healthy female control mice and its disturbances in diabetic GIPRdn transgenic mice, which exhibit an early reduction of beta-cell mass. Pancreata of female control and GIPRdn transgenic mice, aged 10, 45, 90 and 180 days were examined, using state-of-the-art quantitative- stereologicalmethods.Totalisletandbeta-cellvolumes,aswellastheirabsolutenumbersincreasedsignificantlyuntil90 days in control mice, and remained stable thereafter. The mean islet volumes of controls also increased slightly but significantlybetween10and45daysofage,andthenremainedstableuntil180days.Thetotalvolumeofisolatedbeta- cells,anindicatorofisletneogenesis,andthenumberofproliferating(BrdU-positive)isletcellswerehighestin10-day-old controlsanddeclinedsignificantlybetween10and45days.InGIPRdntransgenicmice,thenumbersofisletsandbeta-cells weresignificantlyreducedfrom10daysofageonwardsvs.controls,andnopostnatalexpansionoftotalisletandbeta-cell volumesoccurredduetoareductioninisletneogenesiswhereasearlyislet-cellproliferationandapoptosiswereunchanged as compared to control mice. Insulin secretion in response to pharmacological doses of GIP was preserved in GIPRdn transgenicmice,andseruminsulintopancreaticinsulincontentinresponsetoGLP-1andargininewassignificantlyhigher inGIPRdntransgenicmicevs.controls.Wecouldshowthattheincreaseinisletnumberismainlyresponsibleforexpansion ofisletandbeta-cellmassinhealthycontrolmice.GIPRdn transg