0271-678X27112007NovJ Cereb Blood Flow MetabSupply and demand in cerebral energy metabolism: the role of nutrient transporters.176617911766-91Glucose 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.SimpsonIan AIADepartment of Neural and Behavioral Sciences College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA. ixs10@psu.eduCarruthersAnthonyAVannucciSusan JSJengR01 NS041405NSNINDS NIH HHSUnited StatesNS41405-01NSNINDS NIH HHSUnited StatesR01 DK044888DKNIDDK NIH HHSUnited StatesR01 DK075130-01DKNIDDK NIH HHSUnited StatesR01 DK036081DKNIDDK NIH HHSUnited StatesDK44888DKNIDDK NIH HHSUnited StatesDK36081DKNIDDK NIH HHSUnited StatesP01 HD30704HDNICHD NIH HHSUnited StatesR56 DK036081DKNIDDK NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tReview20070620