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人脑葡萄糖转运的核磁共振氢谱研究

1H NMR studies of glucose transport in the human brain.

作者信息

Gruetter R, Novotny E J, Boulware S D, Rothman D L, Shulman R G

机构信息

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA.

出版信息

J Cereb Blood Flow Metab. 1996 May;16(3):427-38. doi: 10.1097/00004647-199605000-00009.

Abstract

The difference between 1H nuclear magnetic resonance (NMR) spectra obtained from the human brain during euglycemia and during hyperglycemia is depicted as well-resolved glucose peaks. The time course of these brain glucose changes during a rapid increase in plasma glucose was measured in four healthy subjects, aged 18-22 years, in five studies. Results demonstrated a significant lag in the rise of glucose with respect to plasma glucose. The fit of the integrated symmetric Michaelis-Menten model to the time course of relative glucose signals yielded an estimated plasma glucose concentration for half maximal transport, Kt, of 4.8 +/- 2.4 mM (mean +/- SD), a maximal transport rate, Tmax, of 0.80 +/- 0.45 micromol g-1 min-1, and a cerebral metabolic glucose consumption rate (CMR)glc of 0.32 +/- 0.16 micromol g-1 min-1. Assuming cerebral glucose concentration to be 1.0 micromol/g at euglycemia as measured by 13CMR, the fit of the same model to the time course of brain glucose concentrations resulted in Kt = 3.9 +/- 0.82 mM, Tmax = 1.16 +/- 0.29 micromol g-1 min-1, and CMRglc = 0.35 +/- 0.10 micromol g-1 min-1. In both cases, the resulting time course equaled that predicted from the determination of the steady-state glucose concentration by 13C NMR spectroscopy within the experimental scatter. The agreement between the two methods of determining transport kinetics suggests that glucose is distributed throughout the entire aqueous phase of the human brain, implying substantial intracellular concentration.

摘要

从人类大脑在血糖正常和高血糖期间获得的1H核磁共振(NMR)光谱之间的差异表现为分辨率良好的葡萄糖峰。在五项研究中,对4名年龄在18 - 22岁的健康受试者在血浆葡萄糖快速升高期间大脑葡萄糖变化的时间进程进行了测量。结果表明,葡萄糖升高相对于血浆葡萄糖存在显著滞后。将积分对称米氏模型拟合到相对葡萄糖信号的时间进程中,得出半最大转运时的估计血浆葡萄糖浓度Kt为4.8±2.4 mM(平均值±标准差),最大转运速率Tmax为0.80±0.45 μmol g-1 min-1,以及脑代谢葡萄糖消耗率(CMR)glc为0.32±0.16 μmol g-1 min-1。假设通过13C MR测量,血糖正常时脑葡萄糖浓度为1.0 μmol/g,将相同模型拟合到脑葡萄糖浓度的时间进程中,得出Kt = 3.9±0.82 mM,Tmax = 1.16±0.29 μmol g-1 min-1,以及CMRglc = 0.35±0.10 μmol g-1 min-1。在这两种情况下,所得的时间进程在实验误差范围内与通过13C NMR光谱法测定稳态葡萄糖浓度所预测的结果相等。两种测定转运动力学方法之间的一致性表明,葡萄糖分布在人类大脑的整个水相中,这意味着细胞内有相当高的浓度。

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