C-Peptide and Its C-Terminal Fragments Improve Erythrocyte Deformability in Type 1 Diabetes Patients英文文献资料.docVIP

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C-Peptide and Its C-Terminal Fragments Improve Erythrocyte Deformability in Type 1 Diabetes Patients英文文献资料.doc

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C-Peptide and Its C-Terminal Fragments Improve Erythrocyte Deformability in Type 1 Diabetes Patients英文文献资料

HindawiPublishingCorporation ExperimentalDiabetesResearch Volume2008,ArticleID730594,6pages doi:10.1155/2008/730594 ResearchArticle C-PeptideandItsC-TerminalFragmentsImproveErythrocyte DeformabilityinType1DiabetesPatients ThomasHach,1,2ThomasForst,1,3ThomasKunt,4KarinEkberg,5AndreasPfu¨tzner,3andJohnWahren5 1 2 3 4 5 DepartmentofInternalMedicine,UniversityofMainz,55101Mainz,Germany McKinseyCompany,Inc.,AmSandtorkai77,20457Hamburg,Germany InstituteforClinicalResearchandDevelopment,55116Mainz,Germany DepartmentofInternalMedicine,ZayedMilitaryHospital,P.O.Box3740,AbuDhabi,UnitedArabEmirates DepartmentofMolecularMedicineandSurgery,SectionofClinicalPhysiology,KarolinskaInstitute,17177Stockholm,Sweden CorrespondenceshouldbeaddressedtoThomasHach,thomashach@ Received9October2007;Accepted27February2008 RecommendedbySubrataChakrabarti Aims/hypothesis.DatanowindicatethatproinsulinC-peptideexertsimportantphysiologicale?ectsandshowsthecharacteristics of an endogenous peptide hormone. This study aimed to investigate the in?uence of C-peptide and fragments thereof on erythrocytedeformabilityandtoelucidatetherelevantsignaltransductionpathway.Methods.Bloodsamplesfrom23patients with type 1 diabetes and 15 matched healthy controls were incubated with 6.6nM of either human C-peptide, C-terminal hexapeptide,C-terminalpentapeptide,amiddlefragmentcomprisingresidues11–19ofC-peptide,orrandomlyscrambledC- peptide. Furthermore,redblood cells from7patientswere incubated with C-peptide,penta-and hexapeptides with/without additionofouabain,EDTA,orpertussistoxin.Erythrocytedeformabilitywasmeasuredusingalaserdi?ractoscopeintheshear stressrange0.3–60Pa.Results.Erythrocytedeformabilitywasimpairedby18–25%intype1diabeticpatientscomparedtomatched controls in the physiological shear stress range 0.6–12Pa (P .01–.001). C-peptide, penta- and hexapeptide all signi?cantly improved the impaired erythrocyte deformability of type 1 diabetic patients, while the middle fragment and scrambled C- peptidehadnod