Attenuation of Renovascular Damage in Zucker Diabetic Fatty Rat by NWT-03, an Egg Protein Hydrolysate with ACE- and DPP4-Inhibitory Activity 英文参考文献.docVIP

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Attenuation of Renovascular Damage in Zucker Diabetic Fatty Rat by NWT-03, an Egg Protein Hydrolysate with ACE- and DPP4-Inhibitory Activity 英文参考文献.doc

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Attenuation of Renovascular Damage in Zucker Diabetic Fatty Rat by NWT-03, an Egg Protein Hydrolysate with ACE- and DPP4-Inhibitory Activity 英文参考文献

AttenuationofRenovascularDamageinZuckerDiabetic FattyRatbyNWT-03,anEggProteinHydrolysatewith ACE-andDPP4-InhibitoryActivity YumeiWang1,SjoerdLandheer2,WiekH.vanGilst3,AartvanAmerongen4,Hans-PeterHammes1, RobertH.Henning2,LeoE.Deelman2,HendrikBuikema2* 15th Medical Department, Section of Endocrinology, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany, 2Departments of Clinical Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, 3Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, 4Food and Biobased Research, Wageningen University and Research Center, Wageningen, The Netherlands Abstract Background: Dipeptidyl peptidase 4 (DPP4) and angiotensin-converting enzyme (ACE) are important target enzymes in glycemic control and renovascular protection. Here, we studied the effect of NWT-03, an egg protein hydrolysate with DPP4-andACE-inhibitoryactivity,onrenovasculardamageinZuckerdiabeticfatty(ZDF)rats.Comparisonsweremadeto ratstreatedwithvildagliptin(VIL),includedasapositivecontrolfortheeffectofDPP4inhibition. Methods:ZDFratsreceivedNWT-03(1g/kg/day)orVIL(3mg/kg/day)from10to25weeksofage.Metabolicandrenal functions were assessed; the kidney was removed for histological analysis of glomerulosclerosis and expression of pro- inflammatory/fibrotic markers (RT-PCR and Western blotting); and the aorta was removed for studies of endothelium- dependentrelaxation(EDR). Findings:HyperinsulinemicZDFratstypicallydevelopedsignsoftype-2diabetesandrenovasculardamage,asevidenced byalbuminuria,glomerulosclerosis,andimpairedEDR.NeitherNWT-03norVILimprovedmetabolicparameters;forVIL,this wasdespitea5-foldincreaseinglucagon-likepeptide(GLP)-1levels.NWT-03andVILbothreducedrenalinterleukin(Il)-1b/ Il-13mRNAexpressionandglomerulosclerosis.However,onlyNWT-03additionallydecreasedrenaltumornecrosisfactor (TNF)-amRNAandP22phox proteinexpression,reducedalbuminuria