Glycogen provides an important glucose reservoir in the brain since the concentration of glucosyl units stored in glycogen is several fold higher than free glucose available in brain tissue. We have previously reported 3–4 µmol/g brain glycogen content using in vivo 13C magnetic resonance spectroscopy (MRS) in conjunction with [1-13C]glucose administration in healthy humans, while higher levels were reported in the rodent brain. Due to the slow turnover of bulk brain glycogen in humans, complete turnover of the glycogen pool, estimated to take 3–5 days, was not observed in these prior studies. In an attempt to reach complete turnover and thereby steady state 13C labeling in glycogen, here we administered [1-13C]glucose to healthy volunteers for 80 h. To eliminate any net glycogen synthesis during this period and thereby achieve an accurate estimate of glycogen concentration, volunteers were maintained at euglycemic blood glucose levels during [1-13C]glucose administration and 13C-glycogen levels in the occipital lobe were measured by 13C MRS approximately every 12 h. Finally, we fitted the data with a biophysical model that was recently developed to take into account the tiered structure of the glycogen molecule and additionally incorporated blood glucose levels and isotopic enrichments as input function in the model. We obtained excellent fits of the model to the 13C-glycogen data, and glycogen content in the healthy human brain tissue was found to be 7.8 ± 0.3 µmol/g, a value substantially higher than previous estimates of glycogen content in the human brain.
Bibliographical noteFunding Information:
We thank the staff of the Center for MR Research for maintaining and supporting the NMR system and Dr. Gerald Dienel for detailed feedback on our manuscript. This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS) Grant R01 NS035192. The Center for Magnetic Resonance Research is supported by National Institute of Biomedical Imaging and Bioengineering (NIBIB) Grant P41 EB015894, the Institutional Center Cores for Advanced Neuroimaging award P30 NS076408 and National Center for Research Resources (NCRR) Grants S10 RR023730 and S10 RR027290. Amir Moheet is supported by CTSA 5KL2TR000113. Research reported in this publication was also supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
© 2015, Springer Science+Business Media New York.
- C magnetic resonance spectroscopy
- Human brain
- Mathematical modeling