The concentration and metabolism of the primary carbohydrate store in the brain, glycogen, is unknown in the conscious human brain. This study reports the first direct detection and measurement of glycogen metabolism in the human brain, which was achieved using localized 13C NMR spectroscopy. To enhance the NMR signal, the isotopic enrichment of the glucosyl moieties was increased by administration of 80g of 99% enriched [1-13C]glucose in four subjects. 3 h after the start of the label administration, the 13C NMR signal of brain glycogen C1 was detected (0.36±0.07μmol/g, mean±S.D., n=4). Based on the rate of 13C label incorporation into glycogen and the isotopic enrichment of plasma glucose, the flux through glycogen synthase was estimated at 0.17±0.05μmol/(gh). This study establishes that brain glycogen can be measured in humans and indicates that its metabolism is very slow in the conscious human. The noninvasive detection of human brain glycogen opens the prospect of understanding the role and function of this important energy reserve under various physiological and pathophysiological conditions.
Bibliographical noteFunding Information:
We thank the nurses and medical assistants of the General Clinical Research Center for their enthusiastic support of this study, the staff of the Center for MR Research for maintaining and supporting the NMR system, Dr. Kumil Uğurbil for his encouragement and support, Dr. Chaodong Wu Gerald A. Dienel and Nancy F. Cruz for assistance with the biochemical measurement of glycogen in phantoms. The Center for MR Research is in part supported by a National Center for Research Resources (NCRR) biotechnology research resource grant P41RR08079 and the General Clinical Research Center at the University of Minnesota by NCRR grant M01RR00400. This research was supported by NIH grant R21DK58004 (RG), the Juvenile Diabetes Research Foundation research grant 1-722-2001 (RG) and the Whitaker Foundation (RG).
- Brain glycogen