On the basis of previous indirect measurements, skeletal muscle has been implicated as the major site of glucose uptake and it has been suggested that muscle glycogen formation is the dominant pathway. However, direct measurements of the rates of glycogen synthesis have not been possible by previous techniques. We have developed 13C NMR methods to measure directly the rate of human muscle glycogen formation from infused, isotopically labeled [1-13C]glucose. We show that under conditions of imposed hyperglycemia and hyperinsulinemia, a majority of the infused glucose was converted to muscle glycogen in a normal man. This directly shows that muscle is the major site of glucose disposal under these conditions, and provides quantitation of the glucose flux to muscle glycogen.

Optimizing the surface-coil design and spectral-acquisition parameters has led to the observation of the 13C NMR natural abundance glycogen signal in man at 2.1 T. Both the human muscle and hepatic glycogen signals can be detected definitively with a time resolution of -13 min. A IH/'3C concentric surface coil was used. The 1H outer coil was 11 cm in diameter; the 13C inner coil was 8 cm in diameter. The coils were tuned to 89.3 MHz and 22.4 MHz, respectively. The IH coil was used for optimizing field homogeneity (shimming) the magnet and for single-frequency decoupling of the Cl glycogen signal. Total power'deposition from both the transmitter pulse and the continuous wave decoupling did not exceed the Food and Drug Administration guideline of 8 W/kg of tissue. Experiments were done for which healthy subjects returned to the magnets at different times for '3C NMR measurement. The spectral difference between experiments was within the noise in the C, glycogen region. Because of the spectral reproducibility and the signal sensitivity, hepatic glycogen repletion can be followed. Four hours postprandial, hepatic glycogen increases by 3.8 times from the basal fasted state. The hepatic glycogen data correspond directly to previous biopsy results and support the use of 13C NMR as a noninvasive probe of human metabolism.Mammalian cells store glucose as glycogen and expend the latter to meet energy demands. Despite the key role of glycogen, many questions remain about hepatic and muscle glycogen repletion and utilization in man. Our understanding has relied on animal model studies (1, 2) and has rested heavily on experimental data obtained from needle biopsy of human muscle and, sometimes, liver. Animal metabolism, of course, is quite different from human (3), and the invasive nature of needle-biopsy techniques has probably discouraged studies of human glycogen metabolism (4, 5).Recent advances in in vivo NMR have emphasized 31P and 1H and not '3C (6, 7). However, the '3C studies of rats at 8.5 T (8, 9) and rabbit at 1.9 T (10) indicated that the '3C NMR technique can reveal hepatic glycogen signals in vivo. Sillerud and Shulman (8) had shown that the '3C NMR intensities originate from 100% of the glycogen atoms; the visibility was established by hydrolyzing glycogen to glucose and observing that the gain in the glucose intensities equaled the loss in the glycogen intensities. The unexpected nature of this high visibility, coming from glycogen molecules with molecular mass of :10 Da, has prompted other investigators (11,12) to repeat the experiments in live animals. Hence all glycogen molecules in vivo are visible; consequently, with proper calibration, their 13C intensities can be used to determine concentrations.The first natural-abundance 13C glycogen signal from human muscle and liver was observed at 2.1 T (13, 14). Subsequent natural-abundance '3C spectra at 4.7 T confirmed the human muscle results and monitored the changes in glycogen levels with exercise (15). However, the initial '3C spectra at 2.1 T lac...