Natural-abundance 13CNMR studyofglycogen repletion inhuman liver andmuscle

Optimizing thesurface-coil design andspec- tral-acquisition parameters hasledtotheobservation ofthe13C NMRnatural abundance glycogen signal inmanat2.1T.Both thehumanmuscle andhepatic glycogen signals canbedetected definitively withatimeresolution of-13min.A IH/'3C concentric surface coil wasused. The1Houter coil was11cm indiameter; the13Cinner coil was8cmindiameter. Thecoils weretuned to89.3 MHzand22.4 MHz,respectively. TheIH coil wasusedforoptimizing field homogeneity (shimming) the magnet andforsingle-frequency decoupling oftheClglycogen signal. Total power'deposition fromboth thetransmitter pulse andthecontinuous wavedecoupling didnotexceed theFood andDrugAdministration guideline of8 W/kgoftissue. Experiments weredoneforwhich healthy subjects returned to themagnets atdifferent times for'3CNMRmeasurement. The spectral difference between experiments waswithin thenoise in theC,glycogen region. Because ofthespectral reproducibility andthesignal sensitivity, hepatic glycogen repletion canbe followed. Fourhours postprandial, hepatic glycogen increases by3.8times from thebasal fasted state. Thehepatic glycogen datacorrespond directly toprevious biopsy results andsupport theuseof13CNMR asa noninvasive probeofhuman metabolism. Mammalian cells store glucose asglycogen andexpend the latter tomeetenergy demands. Despite thekeyroleof glycogen, manyquestions remain about hepatic andmuscle glycogen repletion andutilization inman.Ourunderstanding hasrelied onanimal modelstudies (1,2)andhasrested heavily onexperimental data obtained fromneedle biopsy of humanmuscle and, sometimes, liver. Animal metabolism, of course, isquite different fromhuman(3), andtheinvasive nature ofneedle-biopsy techniques hasprobably discouraged studies ofhumanglycogen metabolism (4,5). Recent advances ininvivo NMR haveemphasized 31P and 1Handnot'3C(6,7).However, the'3Cstudies ofrats at8.5 T(8,9)andrabbit at1.9T(10) indicated that the'3C NMR technique canreveal hepatic glycogen signals invivo. Sillerud andShulman (8)hadshownthatthe'3CNMR intensities originate from100%oftheglycogen atoms; thevisibility was established byhydrolyzing glycogen toglucose andobserv- ingthat thegain intheglucose intensities equaled theloss in theglycogen intensities. Theunexpected nature ofthis high visibility, coming fromglycogen molecules with molecular massof:10Da,hasprompted other investigators (11, 12) torepeat theexperiments inlive animals. Henceall glycogen molecules invivoarevisible; consequently, withproper calibration, their 13Cintensities canbeusedtodetermine concentrations. Thefirst natural-abundance