Glucose Transport Is Rate Limiting for Skeletal Muscle Glucose Metabolism in Normal and STZ-Induced Diabetic Rats

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1、GlucoseTransportIsRateLimitingforSkeletalMuscleGlucoseMetabolisminNormalandSTZ-lnducedDiabeticRatsFREDERICKH.ZIEL,NATARAJANVENKATESAN,ANDMAYERB.DAVIDSONmulationofintracellularfreeglucoseinskeletalmuscleinTotestthehypothesisthatglucosetransportisratelimitingforskeletalmuscleglucosemetabolism,v

2、itro,whichimpliesthattheprocessofglucosetransportisintracellularfreeglucosewasmeasuredininsituratelimitingforglucosemetabolisminthistissue(4).abdominalwallmuscleandliverthatwererapidlyRecently,invivoexperimentsmeasuringkineticparame-freeze-clampedandremovedfromnormalandtersofglucosedisposalan

3、dthedistributionoflabeledglu-streptozocin-induceddiabetic(STZ-D)Sprague-Dawleycosehavebeeninterpretedtosuggestthatathighinsulinratsexposedtodifferentconcentrationsofserumconcentrationstherate-limitingstepinskeletalmuscleshiftsinsulinandglucoseachievedby90-minglucosefromglucosetransporttosomep

4、osttransportevent(5-7).clamps.Threegroupsofanesthetizednormal(n=17)ToclarifywhetherglucosetransportisindeedratelimitingandthreegroupsofSTZ-D(n=19)animalswereforskeletalmuscleglucosemetabolisminvivoacrossphys-studied.Ineachgroup,infusionswereadjustedtoexposeratstobasal,euglycemic-hyperinsuline

5、mic,iologicandsupraphysiologicinsulinandglucoseconcen-andhyperglycemic-hyperinsulinemicconditions.Finaltrations,wemeasuredintracellularfreeglucoseininsitusteady-stateserumglucoseandinsulinconcentrationsskeletalmusclefromnormalanesthetizedratsrenderedhy-(mean±SE)achievedinthesixgroupsrangedfro

6、mperglycemicandhyperinsulinemicbyaglucoseclamptech-112±2to467±26mg/dlandfrom5.8±1.9tonique.Tofurtherclarifywhetherglucosetransportremains3644±116

7、xU/ml,respectively.Intracellularfree-ratelimitinginamodelofdiabeteswithknowninsulinre-glucosecontentofalltissuewascalculatedfromtotalsistance(8,9),

8、atleastpartlyduetoadeficitinbothglucose-tissueglucosecontentminusthecontributionoftransporter-proteinnumberandglucosetransportactivityglucoseinextracellularwaterestimatedwith14(10),wehaveperformedparallelexperimentsinstreptozo-[C]inulin.Intra