Metabolic Profiling of the Response to an Oral Glucose Tolerance Test Detects Subtle Metabolic Changes 英文参考文献.docVIP

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Metabolic Profiling of the Response to an Oral Glucose Tolerance Test Detects Subtle Metabolic Changes 英文参考文献.doc

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Metabolic Profiling of the Response to an Oral Glucose Tolerance Test Detects Subtle Metabolic Changes 英文参考文献

MetabolicProfilingoftheResponsetoanOralGlucose ToleranceTestDetectsSubtleMetabolicChanges SuzanWopereis1*,CarinaM.Rubingh1,MarjanJ.vanErk1,ElwinR.Verheij1,TrinettevanVliet1¤, NicoleH.P.Cnubben1,AgeK.Smilde1,2,JanvanderGreef1,BenvanOmmen1,HenkF.J.Hendriks1 1DepartmentQualityofLife,TNO,Zeist,theNetherlands,2BiosystemsDataAnalysis,SwammerdamInstituteforLifeSciences,UniversityofAmsterdam,Amsterdam,the Netherlands Abstract Background: The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronicinflammationinoverweightsubjectsisthoughttoplayanimportantroleindiseasedevelopment.Noveltoolsto understandtheseprocessesareneeded.Metabolicprofilingisonesuchtoolthatcanprovidenovelinsightsintotheimpact oftreatmentsonmetabolism. Methodology:Tostudythemetabolicchangesinducedbyamildanti-inflammatorydrugintervention,plasmametabolic profilingwasappliedinoverweighthumanvolunteerswithelevatedlevelsoftheinflammatoryplasmamarkerC-reactive protein.Liquidandgaschromatographymassspectrometricmethodswereusedtodetecthighandlowabundantplasma metabolites both in fasted conditions and during an oral glucose tolerance test. This is based on the concept that the resilienceofthesystemcanbeassessedafterperturbingahomeostaticsituation. Conclusions:Metabolicchangesweresubtleandwereonlydetectedusingmetabolicprofilingincombinationwithanoral glucosetolerancetest.Therepeatedmeasurementsduringtheoralglucosetolerancetestincreasedstatisticalpower,but the metabolic perturbation also revealed metabolites that respond differentially to the oral glucose tolerance test. Specifically,multiplemetabolicintermediatesoftheglutathionesynthesispathwayshowedtime-dependentsuppressionin response to the glucose challenge test. The fact that this is an insulin sensitive pathway suggests that inflammatory modulationmayalterinsulinsignalinginoverweightmen. Citation:WopereisS,RubinghCM,vanErkMJ,VerheijER,vanVlietT,etal.(2009)MetabolicProfilingoftheResponsetoanOralGlucoseTolerance