Experimental Study on the Insulin-Sensitivit y-Increasing Effect of Berberine in Insulin Resistant Rat ModelsGAOCong-rong,ZHANGJia- qingandHUANGQing-ling(DeportmentOfEndocrino logy,ChanghaiHospital,Shanghai,200433)Abstr act:Objective:Toobservetheeffectsofberberin eoninsulinsensitivityinhigh-fat-fedrats.Met hods:Beforeandafteringestingberberine,gluco seinsulintolerancetestwasusedtomeasurethein sulinsensitivity,andtodeterminethefastingbl oodglucose,insulin,bloodlipidandmuscletrigl yceridecontent.ResultS:Comparedwithnormally fedrats,high-fat-fedratshadtheirinsulinsens itivitylowered(Kvalue5.02±1.08 vs8.72±0.91, P<0.005),levelofliverglycogendecreasedandle velsoffastingbloodglucose,insulin,lipid and muscletriglyceridecontentraised.Berberinean dmetforminimprovedinsulinresistance(Kvalue6 .31±0.95and6.24±0.65)andliverglycogenleveli ninsulinresistantmodels,thoughtheyhadnoeffe ctonblood glucose,insulin,lipidlevelsandmus cletriglyceridedepots.Conclusion:Itisconfir medthatberberinehadsimilareffectinraisingin sulinsensitivityofhigh-fat-fedrats.Keywords :berberine,metformin,insulinsensitivity,ins ulinresistanceItisk.o.n(1'2)thathigh-fatfoo dcanleadtoaccumulationoftriglyceride(TG)inm uscleandinsulinresistance(IR).IRisan'import antfactorinpathophysiologyofnon-insulin-dep endentdiabetesmellitusandinsulinsensitizers arenowbeingstudiedclinically.Thoughthereisr eportthatmetformincanalsoraiseinsulinsensit ivity,thereisnoneaboutanyChinesemedicinalhe rboringredientstudiedandprovedtohaveeffecto ninsulinsensitivity.Berberinehasbeenreporte dtohavetheeffectsofreducingbloodglucoseandi mprovingglucosetoleranceofspontaneousdiabet icrats(3).ButwhetheritcanimproveiRinratrema insunknown.OurstudywasmeanttobeatestontheiR reducingeffectsofberberineonratmodelsinduce dbyhighfatfeeding.METHODSDabMetforminisapro ductofKunshanPharmaceuticalFactoryandberber ineisanextractionbyTraditionalChineseHerbsD epartmentOfChanghaiHospital.alIgnsedbotThir tymaleWistarratsaged50--60daysandweighing24 0gweredividedrandomlyintofourgroups:thenorm alcontrolgroup(n=7),thehigh--fat--fedcontro lgroup(n=7),theberberine--treatedgroup(n=8) andthemetformin-treatedgroup(n=8).Eachratto okcalories310KJ/day.Thenormalcontrolgroupwa sfedwithstandardratfood(11%ofcaloriesinfat, 61%incarbohydrate),theothergroupswerefedwit hhighfatfeed(59%ofcaloriesinlard)(4).Highfa tfeedwasprepareddaily.Berberineormetformin( 100mg/kg)wereaddedintothefeedforthetreatmen tgroupsthroughgastrogavageat9a.m.everyday,w hiletheothertwocontrolgroupsweregivenequala mountofsaline.Allgroupswerefreetodrinkwater duringtheexperiment.Theexperimentlasted1mon th.P8f ̄rsedM6tToDetermineBodyWeight,Stoolan dAInountofFoodintakeAssayofFastingBloodGluc ose(FBG),Immunoreactiveinsulin(IRI)andBlood LipidLevelFastingbloodsamplesweretakenfromt heorbitalveinonthe30thdayofexperiment.Blood glucoseconcentrationwasmeasuredbyglucoseoxi dasemethod.Insulinwasdeterminedbydoubled-an tibodyRIA.Bloodlipidwasassayedwiththecolori metricenzymaticprocedure.AssayofinsulinSens itivityGlucose-insulintolerancetest(5)waspe rformedonthe31stdayofexperiment.Theratswere anesthetizedinthenonfastingstatebyanintrape ritonealinjectionofsodiumphenobarbital(50mg /kg).Twocatheterswereinsertedviafemoralvein andartery,andthenglucose(700mg/kg)wasinject edintothefemoralveinwitharegularinsulininje ctionofadoseof0.175u/kgfollowingcloseuponit .Bloodsampleswerecollected3,6,9,12and15minu tesaftertheinsulininjection,fromthefemorala rterytodeterminetheglucoselevels.Insulinsen sitivityindex(K)wascalculatedfrom3--15minut esglucoseloweringrate.Afterthistest,theratw assacrificed,andliverandredquadricepswereim mediatelyremovedandfrozenin--20t.AssayofLiv erGlycogenandMuscleTGLiverglycogenwasmeasur edbyVanderVies'smethod(6).MuscleTGwasmeasur edbyStorlien'sm.thod(1).RESULtsOhs ̄OfBacWei ght.StOOledAmOUntafFialInalDecreasedfeedint akewasnotedinthetreatmentgroups.Thestoolwas looserinthethreehigh-fat-fedgroupsthaninthe normalcontrolgroupwiththatofthemetformintreatedgrouptheloosest.Thebodyweightsofthethreehigh-fat-fedgroupsweresimilartothatofthenormalcontrolgroup.Butcomparedwithhigh-fat-fe
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