Calpain-10 Expression Is Elevated in Pancreatic Islets from Patients with Type 2 Diabetes 英文参考文献.docVIP

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Calpain-10 Expression Is Elevated in Pancreatic Islets from Patients with Type 2 Diabetes 英文参考文献.doc

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Calpain-10 Expression Is Elevated in Pancreatic Islets from Patients with Type 2 Diabetes 英文参考文献

Calpain-10ExpressionIsElevatedinPancreaticIslets fromPatientswithType2Diabetes CharlotteLing1*,LeifGroop1,SilviaDelGuerra2,RobertoLupi2 1Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, Clinical Research Centre (CRC), Malmo¨, Sweden, 2Department ofEndocrinologyand Metabolism,MetabolicUnit,UniversityofPisa,Pisa,Italy Abstract Background: Calpain-10 was the first gene to be identified influencing the risk of type 2 diabetes (T2D) by positioning cloning.Studiesinb-celllinesandrodentisletssuggestthatcalpain-10mayactasaregulatorofinsulinsecretion.However, itsroleinhumanpancreaticisletsremainsunclear.Theaimofthisstudywastoexamineifcalpain-10expressionisalteredin isletsfrompatientswithT2Dandifthetranscriptlevelcorrelateswithinsulinrelease.Wealsotestedifpolymorphismsinthe CAPN10geneareassociatedwithgeneexpressionandinsulinsecretioninvitro. Methodology/Principal Findings: Calpain-10 mRNA expression was analysed in human pancreatic islets from 34 non- diabeticand10T2Dmulti-organdonors.CAPN10SNP-43andSNP-44weregenotypedandrelatedtogeneexpressionand insulinreleaseinresponsetoglucose,arginineandglibenclamide.ThemRNAlevelofcalpain-10waselevatedby64%in pancreaticisletsfrompatientswithT2Dcomparedwithnon-diabeticdonors(P=0.01).Moreover,thecalpain-10expression correlatedpositivelywitharginine-stimulatedinsulinreleaseinisletsfromnon-diabeticdonors(r=0.45,P=0.015).However, thiscorrelationwaslostinisletsfrompatientswithT2D(r=0.09;P=0.8).TheG/GvariantofSNP-43wasassociatedwith reducedinsulinreleaseinresponsetoglucose(P#0.04)innon-diabeticdonors. Conclusions:Whilecalpain-10expressioncorrelateswithinsulinreleaseinnon-diabetichumanislets,thiscorrelationislost inT2Dsuggestingthatastimulatoryeffectofcalpain-10couldbelostinpatientswithT2D. Citation:LingC,GroopL,DelGuerraS,LupiR(2009)Calpain-10ExpressionIsElevatedinPancreaticIsletsfromPatientswithType2Diabetes.PLoSONE4(8): e6558.doi:10.1371/journal.pone.0006558 Editor:KathrinMaedler,UniversityofBremen,Germany Recei