Revisiting Glycogen Content in the Human Brain.
Revisiting Glycogen Content in the Human Brain.
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DOI：
10.1007/s11064-015-1664-4
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发表时间：
2015-12
影响因子：
4.4
通讯作者：
Seaquist ER
中科院分区：
文献类型：
--
作者：
Öz G;DiNuzzo M;Kumar A;Moheet A;Seaquist ER
糖原在大脑中提供了一个重要的葡萄糖储存库，因为储存在糖原中的葡萄糖基单位的浓度比脑组织中可用的游离葡萄糖高几倍。我们之前报道了在健康人类中使用体内13C磁共振波谱（MRS）结合[1-13C]葡萄糖给药的3-4µmol/g脑糖原含量，而在啮齿动物的大脑中报道了更高的水平。由于人体大量脑糖原的代谢缓慢，在之前的研究中没有观察到糖原库的完全代谢，估计需要3-5天。为了实现糖原的完全转化，从而使糖原中的13C标记达到稳定状态，我们给健康志愿者服用[1-13C]葡萄糖80小时。为了消除在此期间的任何净糖原合成，从而获得准确的糖原浓度估计，在给糖期间，志愿者保持在正血糖水平，并且大约每12小时用13C MRS测量枕叶13C-糖原水平。最后，我们将数据与最近开发的生物物理模型进行拟合，该模型考虑了糖原分子的分层结构，并将血糖水平和同位素富集作为模型的输入函数。我们获得了与13c -糖原数据非常吻合的模型，发现健康人脑组织中的糖原含量为7.8±0.3µmol/g，大大高于先前人脑中糖原含量的估计。
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 hours. 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 hours. 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.