Albiglutide, a Long Lasting Glucagon-Like Peptide-1 Analog, Protects the Rat Heart against IschemiaReperfusion Injury Evidence for Improving Cardiac Metabolic Efficiency 英文参考文献.docVIP
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Albiglutide, a Long Lasting Glucagon-Like Peptide-1 Analog, Protects the Rat Heart against IschemiaReperfusion Injury Evidence for Improving Cardiac Metabolic Efficiency 英文参考文献
Albiglutide,aLongLastingGlucagon-LikePeptide-1
Analog,ProtectstheRatHeartagainstIschemia/
ReperfusionInjury:EvidenceforImprovingCardiac
MetabolicEfficiency
WeikeBao1,KarpagamAravindhan1,HasanAlsaid2,ThimmaiahChendrimada2,MatthewSzapacs3,
DavidR.Citerone3,MarkR.Harpel1,RobertN.Willette1,JohnJ.Lepore1,BeatM.Jucker1*
1HeartFailureDiscoveryPerformanceUnit,MetabolicPathwaysandCardiovascularTherapyAreaUnit,GlaxoSmithKline,KingofPrussia,Pennsylvania,UnitedStatesof
America,2ClinicalImagingCenter,GlaxoSmithKline,KingofPrussia,Pennsylvania,UnitedStatesofAmerica,3PlatformTechnologyandScience,GlaxoSmithKline,Kingof
Prussia,Pennsylvania,UnitedStatesofAmerica
Abstract
Background:Thecardioprotectiveeffectsofglucagon-likepeptide-1(GLP-1)andanalogshavebeenpreviouslyreported.
Wetestedthehypothesisthatalbiglutide,anovellonghalf-lifeanalogofGLP-1,mayprotecttheheartagainstI/Rinjuryby
increasingcarbohydrateutilizationandimprovingcardiacenergeticefficiency.
Methods/Principal Findings: Sprague-Dawley rats were treated with albiglutide and subjected to 30min myocardial
ischemiafollowedby24hreperfusion.Leftventricleinfarctsize,hemodynamics,functionandenergeticsweredetermined.
Inaddition,cardiacglucosedisposal,carbohydratemetabolismandmetabolicgeneexpressionwereassessed.Albiglutide
significantlyreducedinfarctsizeandconcomitantlyimprovedpost-ischemichemodynamics,cardiacfunctionandenergetic
parameters.Albiglutidemarkedlyincreasedbothinvivoandexvivocardiacglucoseuptakewhilereducinglactateefflux.
Analysisofmetabolicsubstrateutilizationdirectlyintheheartshowedthatalbiglutideincreasedtherelativecarbohydrate
versusfatoxidationwhichinpartwasduetoanincreaseinbothglucoseandlactateoxidation.Metabolicgeneexpression
analysisindicatedupregulationofkeyglucosemetabolismgenesinthenon-ischemicmyocardiumbyalbiglutide.
Conclusion/Significance: Albiglutide reduced myocardial infarct size and improved cardiac function and energetics
following myocardial I/R injury. The observed benefits were associated with enha
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