糖尿病治疗三重奏到八重奏.ppt

***Elevatedratesofbasalhepaticglucoseoutput(bHGO)aresignificantlycorrelatedwiththefastingserumglucose(FSG)levelinsubjectswithnon-insulin-dependentdiabetesmellitus(NIDDM).ThisobservationsuggeststhatbHGOisamajordeterminantoftheseverityofthediabeticstateinthesesubjects.Inaddition,basalglucagonlevels(bGL)arehigherinthesediabeticsthanincontrolsubjects,despitetheconcurrentbasalhyperglycemiaandhyperinsulinemia,twofactorsknowntosuppressglucagonsecretion.AlthoughbGLisresponsibleforsustainingtwo-thirdsofbHGOinnormalhumans,itsroleinsustainingelevatedratesofbHGOinNIDDMhasnotbeenpreviouslydefined.Tothisend,wehavestudied13normaland10NIDDMsubjects;meanFSGlevelswere90+/-2and262+/-21mg/dl,respectively(Plessthan.001).Themeanfastingseruminsulinandglucagonlevelswerehigherinthediabeticsthaninthecontrols:17+/-2vs.9+/-1microU/ml(Plessthan.01)and208+/-37vs.104+/-15pg/ml(Plessthan.01),respectively.Onseparatedays,HGOwasassessedisotopically(with3-[3H]glucose)inthebasalstateandduringinfusionofsomatostatin(SRIF)(600micrograms/h)aloneandinconjunctionwithreplacementinfusionsofglucoseandinsulin.TheresultsdemonstratethatbHGOishigherindiabeticsthanincontrols(145+/-12vs.89+/-3mgXm-2Xmin-1,Plessthan.01);duringinfusionofSRIFalone,HGOwassuppressedby25%(Plessthan.05)and34%(Plessthan.05)ofthebasalvalueincontrolsanddiabetics,respectively;whenthestudieswererepeatedwithglucoselevelsheldconstantatorneartheFSGlevelbytheglucose-clamptechnique,thepatternanddegreeofHGOsuppressionwassimilartothatobtainedbyinfusionofSRIFalone;duringisolatedglucagondeficiency(SRIF+insulin,5mUXm-2min-1,withserumglucosemaintainedatbasallevel),HGOwassuppressedby71+/-8%ofthebasalvalueincontrols(Plessthan.00