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首页> 外文期刊>Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism >Supply and demand in cerebral energy metabolism: the role of nutrient transporters.
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Supply and demand in cerebral energy metabolism: the role of nutrient transporters.

机译：脑能量代谢中的供求：营养转运蛋白的作用。

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摘要

Glucose is the obligate energetic fuel for the mammalian brain, and most studies of cerebral energy metabolism assume that the majority of cerebral glucose utilization fuels neuronal activity via oxidative metabolism, both in the basal and activated state. Glucose transporter (GLUT) proteins deliver glucose from the circulation to the brain: GLUT1 in the microvascular endothelial cells of the blood-brain barrier (BBB) and glia; GLUT3 in neurons. Lactate, the glycolytic product of glucose metabolism, is transported into and out of neural cells by the monocarboxylate transporters (MCT): MCT1 in the BBB and astrocytes and MCT2 in neurons. The proposal of the astrocyte-neuron lactate shuttle hypothesis suggested that astrocytes play the primary role in cerebral glucose utilization and generate lactate for neuronal energetics, especially during activation. Since the identification of the GLUTs and MCTs in brain, much has been learned about their transport properties, that is capacity and affinity for substrate, which must be considered in any model of cerebral glucose uptake and utilization. Using concentrations and kinetic parameters of GLUT1 and -3 in BBB endothelial cells, astrocytes, and neurons, along with the corresponding kinetic properties of the MCTs, we have successfully modeled brain glucose and lactate levels as well as lactate transients in response to neuronal stimulation. Simulations based on these parameters suggest that glucose readily diffuses through the basal lamina and interstitium to neurons, which are primarily responsible for glucose uptake, metabolism, and the generation of the lactate transients observed on neuronal activation.
机译：葡萄糖是哺乳动物大脑的专性能量燃料，大多数脑能量代谢研究都认为，大部分的大脑葡萄糖利用都通过氧化代谢在基础状态和激活状态下促进神经元活动。葡萄糖转运蛋白（GLUT）将葡萄糖从循环系统输送到大脑：GLUT1位于血脑屏障（BBB）和神经胶质细胞的微血管内皮细胞中;神经元中的GLUT3。乳酸是葡萄糖代谢的糖酵解产物，通过单羧酸盐转运蛋白（MCT）：BBB中的MCT1和星形胶质细胞以及神经元中的MCT2转运进和流出神经细胞。星形胶质细胞-神经元乳酸穿梭假说的提议表明，星形胶质细胞在脑葡萄糖利用中起主要作用，并为神经元能量产生乳酸，特别是在激活过程中。自从确定了大脑中的GLUT和MCT以来，人们已经学到了很多关于它们的转运特性的知识，即对底物的容量和亲和力，在任何模型的大脑葡萄糖吸收和利用模型中都必须考虑这些特性。使用BBB内皮细胞，星形胶质细胞和神经元中GLUT1和-3的浓度和动力学参数，以及MCT的相应动力学特性，我们已经成功地对脑葡萄糖和乳酸水平以及响应神经元刺激的乳酸瞬变进行了建模。基于这些参数的模拟表明，葡萄糖易于通过基底层和间质扩散至神经元，这主要负责葡萄糖的摄取，代谢以及在神经元激活时观察到的乳酸瞬变的产生。

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