Glucose transporter proteins in brain: Delivery of glucose to neurons and glia

Vannucci, Susan J.; Maher, Frances A.; Simpson, Ian A.

doi:10.1002/(sici)1098-1136(199709)21:1<2::aid-glia2>3.0.co;2-c

Cited by 580 publications

(410 citation statements)

References 123 publications

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“…This assumption is supported by isolated cell studies that have shown high glucose transport activity on neurons and glia (Lund-Andersen 1979;Vannucci et al, 1997). The in vivo magnetic resonance spectroscopy study of Gruetter et al (1996) found a significantly slower time course in the increase of brain glucose relative to plasma glucose during a rapid glucose infusion, which agreed with the kinetics predicted for uniform glucose distribution between brain compartments.…”

Section: Glucose Transport In Human Brain 489supporting

confidence: 53%

Differentiation of Glucose Transport in Human Brain Gray and White Matter

Graaf

Pan

Telang

et al. 2001

J Cereb Blood Flow Metab

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Summary:Localized 1 H nuclear magnetic resonance spectroscopy has been applied to determine human brain gray matter and white matter glucose transport kinetics by measuring the steady-state glucose concentration under normoglycemia and two levels of hyperglycemia. Nuclear magnetic resonance spectroscopic measurements were simultaneously performed on three 12-mL volumes, containing predominantly gray or white matter. The exact volume compositions were determined from quantitative T 1 relaxation magnetic resonance images. The absolute brain glucose concentration as a function of the plasma glucose level was fitted with two kinetic transport models, based on standard (irreversible) or reversible MichaelisMenten kinetics. The steady-state brain glucose levels were similar for cerebral gray and white matter, although the white matter levels were consistently 15% to 20% higher. The ratio of the maximum glucose transport rate, V max , to the cerebral metabolic utilization rate of glucose, CMR Glc , was 3.2 ± 0.10 and 3.9 ± 0.15 for gray matter and white matter using the standard transport model and 1.8 ± 0.10 and 2.2 ± 0.12 for gray matter and white matter using the reversible transport model. The Michaelis-Menten constant K m was 6.2 ± 0.85 and 7.3 ± 1.1 mmol/L for gray matter and white matter in the standard model and 1.1 ± 0.66 and 1.7 ± 0.88 mmol/L in the reversible model. Taking into account the threefold lower rate of CMR Glc in white matter, this finding suggests that blood-brain barrier glucose transport activity is lower by a similar amount in white matter. The regulation of glucose transport activity at the blood-brain barrier may be an important mechanism for maintaining glucose homeostasis throughout the cerebral cortex.

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Section: Glucose Transport In Human Brain 489supporting

confidence: 53%

Differentiation of Glucose Transport in Human Brain Gray and White Matter

Graaf

Pan

Telang

et al. 2001

J Cereb Blood Flow Metab

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“…The mRNA for insulin-responsive GLUT4 was expressed in about half of all neurons, but there were no significant intergroup differences in expression (Table 3). The possibility that neuronal glucosensing might be regulated by insulin's acting on GLUT4, as it is in peripheral tissues (34,35,52), was raised by the coexpression of GLUT4 and INS-R mRNA in 40 -75% of all neurons, regardless of their glucosensing properties (Table 3). Because there were no significant intergroup differences in coexpression, it is less likely that insulin-mediated glucose uptake might serve as an alternate mechanism of glucosensing.…”

Section: Resultsmentioning

confidence: 99%

Physiological and Molecular Characteristics of Rat Hypothalamic Ventromedial Nucleus Glucosensing Neurons

et al. 2004

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To evaluate potential mechanisms for neuronal glucosensing, fura-2 Ca 2؉ imaging and single-cell RT-PCR were carried out in dissociated ventromedial hypothalamic nucleus (VMN) neurons. Glucose-excited (GE) neurons increased and glucose-inhibited (GI) neurons decreased intracellular Ca 2؉ ([Ca 2؉ ] i ) oscillations as glucose increased from 0.5 to 2.5 mmol/l. The Kir6.2 subunit mRNA of the ATP-sensitive K ؉ channel was expressed in 42% of GE and GI neurons, but only 15% of nonglucosensing (NG) neurons. Glucokinase (GK), the putative glucosensing gatekeeper, was expressed in 64% of GE, 43% of GI, but only 8% of NG neurons and the GK inhibitor alloxan altered [Ca 2؉ ] i oscillations in ϳ75% of GK-expressing GE and GI neurons. Insulin receptor and GLUT4 mRNAs were coexpressed in 75% of GE, 60% of GI, and 40% of NG neurons, although there were no statistically significant intergroup differences. Hexokinase-I, GLUT3, and lactate dehydrogenase-A and -B were ubiquitous, whereas GLUT2, monocarboxylate transporters-1 and -2, and leptin receptor and GAD mRNAs were expressed less frequently and without apparent relationship to glucosensing capacity. Thus, although GK may mediate glucosensing in up to 60% of VMN neurons, other regulatory mechanisms are likely to control glucosensing in the remaining ones. Diabetes 53:549 -559, 2004

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“…Glucose transport from blood into the brain is mediated by a facilitated diffusion-type transport system, that is members of the GLUT supergene family of integral membrane proteins (Maher et al, 1994;Vannucci et al, 1997;Shepherd and Kahn, 1999). Tissue-specific expression of one or more members determines the rate of glucose entry into the cell.…”

Section: Discussionmentioning

confidence: 99%

“…As brain glucose metabolism could be adversely affected in some neurodegenerative disorders, including stressrelated neuropsychopathologies (reviewed in Peppard et al (1990), Hoyer (2000), Weinstock and Shoham (2004), Peters et al (2004)), we hypothesized that one mechanism of PPARg agonists' protection during stress exposure could be related to an increase in the cerebral metabolism of glucose. The delivery of glucose within the brain is mediated primarily by GLUT-1, present in the blood-brain barrier and in astrocytes and by GLUT-3 present in neurons (Vannucci et al, 1997;Pellerin, 2005). As 85% of the energy expenditure of the brain occurs in neurons (Attwell and Laughlin, 2001), and glucose is almost the only fuel used by the organ, we tested the possibility that the preventive effects of PPARg agonists are through glucose transporters, possibly through the neuronal component, GLUT-3.…”

Section: Introductionmentioning

confidence: 99%

Effects of Peroxisome Proliferator-Activated Receptor Gamma Agonists on Brain Glucose and Glutamate Transporters after Stress in Rats

García‐Bueno

Caso

Perez‐Nievas

et al. 2006

Neuropsychopharmacol

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Repeated stress causes an energy-compromised status in the brain, with a decrease in glucose utilization by the brain cells, which might account for excitotoxicity processes seen in this condition. In fact, brain glucose metabolism mechanisms are impaired in some neurodegenerative disorders, including stress-related neuropsychopathologies. More recently, it has been demonstrated that some synthetic peroxisome proliferator-activated receptor gamma (PPARg) agonists increase glucose utilization in rat cortical slices and astrocytes, as well as inhibit brain oxidative damage after repeated stress, which add support for considering these drugs as potential neuroprotective agents. To assess if stress causes glucose utilization impairment in the brain and to study the mechanisms by which this effect is achieved, young-adult male Wistar rats (control and immobilized for 6 h during 7 or 14 consecutive days, S7, S14) were i.p. injected with the natural ligand 15-deoxy-D-12,14-prostaglandin J 2 (PGJ 2 , 120 mg/kg) or the high-affinity ligand rosiglitazone (RG, 3 mg/kg) at the onset of stress. Repeated immobilization during 1 or 2 weeks produces a decrease in brain cortical synaptosomal glucose uptake, and this effect was prevented by treatment with both natural and synthetic PPARg ligands by restoring protein expression of the neuronal glucose transporter, GLUT-3 in membrane fractions. On the other hand, treatment with PPARg ligands prevents stress-induced ATP loss in rat brain. Finally, repeated immobilization stress also produces a decrease in brain cortical synaptosomal glutamate uptake, and this effect was prevented by treatment with PPARg ligands by restoring synaptosomal protein expression of the glial glutamate transporter, EAAT2. In summary, our results demonstrate that 15d-PGJ 2 and the thiazolidinedione rosiglitazone increase neuronal glucose metabolism, restore brain ATP levels and prevent the impairment in glutamate uptake mechanisms induced by exposure to stress, suggesting that this class of drugs may be therapeutically useful in conditions in which brain glucose levels or availability are limited after exposure to stress.

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Glucose transporter proteins in brain: Delivery of glucose to neurons and glia

Cited by 580 publications

References 123 publications

Differentiation of Glucose Transport in Human Brain Gray and White Matter

Differentiation of Glucose Transport in Human Brain Gray and White Matter

Physiological and Molecular Characteristics of Rat Hypothalamic Ventromedial Nucleus Glucosensing Neurons

Effects of Peroxisome Proliferator-Activated Receptor Gamma Agonists on Brain Glucose and Glutamate Transporters after Stress in Rats

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