Facilitated glucose transporter protein type 1 (GLUT1) deficiency syndrome: impaired glucose transport into brain – a review

Klepper, Jörg; Voït, Thomas

doi:10.1007/s00431-002-0939-3

Cited by 161 publications

(144 citation statements)

References 75 publications

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“…The mammalian homologue GLUT1, which is found in erythrocytes and the epithelial cells that form the bloodbrain barrier, mediates the majority uptake of glucose into brain through the blood-brain barrier [19]. GLUT1-deficiency syndrome (GLUT1DS), which results in an inadequate energy supply to brain, manifests as delayed neurological development and other neurological problems [20,21].…”

mentioning

confidence: 99%

Mammalian glucose permease GLUT1 facilitates transport of arsenic trioxide and methylarsonous acid

Liu

Sánchez

Jiang

et al. 2006

Biochemical and Biophysical Research Communications

121

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Arsenic exposure is associated with hypertension, diabetes and cancer. Some mammals methylate arsenic. Saccharomyces cerevisiae hexose permeases catalyze As(OH) 3 uptake. Here we report that mammalian glucose transporter GLUT1 catalyzes As(OH) 3 and CH 3 As(OH) 2 uptake in yeast or in Xenopus laevis öocytes. Expression of GLUT1 in a yeast lacking other glucose transporters allows for growth on glucose. Yeast expressing yeast HXT1 or rat GLUT1 transport As(OH) 3 and CH 3 As (OH) 2 . The K m of GLUT1 is to 1.2 mM for CH 3 As(OH) 2 , compared to a K m of 3 mM for glucose. Inhibition between glucose and CH 3 As(OH) 2 is noncompetitive, suggesting differences between the translocation pathways of hexoses and arsenicals. Both human and rat GLUT1 catalyze uptake of both As(OH) 3 and CH 3 As(OH) 2 in öocytes. Thus GLUT1 may be a major pathway uptake of both inorganic and methylated arsenicals in erythrocytes or the epithelial cells of the blood-brain barrier, contributing to arsenic-related cardiovascular problems and neurotoxicity.Arsenic ranks first on the United States Government's Comprehensive Environmental Response, Compensation, and Liability (Superfund) Act Priority List of Hazardous Substances . In response to the Safe Water Drinking Act, the United States Environmental Protection Agency has set the allowable level of arsenic in drinking water at 10 ppb , which is less than the level in the water supplies of many U.S. municipalities . In addition, the Environmental Protection Agency's Office of Pesticide Programs is concerned with exposure to the organic arsenicals methylarsenic acid and dimethylarsenic acid, pentavalent arsenicals used as pesticides and herbicides .Health effects associated with arsenic exposure include cardiovascular and peripheral vascular disease, neurological disorders, diabetes mellitus and various cancers, including liver, bladder, kidney and skin [1][2][3]. Arsenic trioxide, which is As 2 O 3 in the solid, anhydrous form and As (OH) 3 in solution at physiological pH [4], is used clinically as a chemotherapeutic drug for treatment of acute promyelocytic leukemia [5]. Although epidemiological studies demonstrated that arsenic exposure is associated with a high frequency of circulatory and neurological problems [2,6,7], how arsenic causes non-cancer-related diseases is far from clear. Here we report that GLUT1 facilitates uptake of As(OH) 3 and CH 3 As(OH) 2 using heterologous expression in S. cerevisiae and X. laevis öocytes. S. cerevisiae is a valuable model system for structure-function studies of mammalian membrane proteins such as GLUT1 [22,23]. A yeast strain with low uptake of As(OH) 3 and CH 3 As(OH) 2 was constructed by deletion of all 18 hexose transporters, FPS1, which encodes an aquaglyceroporin that facilitates As(OH) 3 influx, and ACR3, the gene for an...

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mentioning

confidence: 99%

Mammalian glucose permease GLUT1 facilitates transport of arsenic trioxide and methylarsonous acid

Liu

Sánchez

Jiang

et al. 2006

Biochemical and Biophysical Research Communications

121

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“…2). However, there appears to be no correlation between 3-OMG uptake values in erythrocytes and phenotypic severity (Klepper et al, 2002;Wang et al, 2005 Zonisamide is a broad-spectrum antiepileptic drug that has been used to treat patients with partial or generalized seizures (Ohtahara, 2006). Although several antiepileptic drugs have been shown to inhibit GLUT1 function, the effects of zonisamide on GLUT1 function remained to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…A ketogenic diet has been suggested as the treatment for patients with GLUT1 deficiency syndrome because ketones enter the brain independent of GLUT1-mediated transport and serve as an alternative fuel for the brain (De Vivo et al, 1991;Nordli and De Vivo, 1997;Klepper and Voit, 2002). Although the ketogenic diet may effectively control the seizures, a subgroup of patients requires add-on anticonvulsant therapy.…”

Section: Introductionmentioning

confidence: 99%

Molecular analysis and anticonvulsant therapy in two patients with glucose transporter 1 deficiency syndrome: A successful use of zonisamide for controlling the seizures

et al. 2008

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“…The GLUT family includes 12 genes encoding 12 GLUT proteins (Vannucci et al, 1997;Klepper and Voit, 2002). Various members of this membrane protein family have been detected in brain (GLUT-1, GLUT-3 and GLUT-5), but the initial glucose transport step across the BBB is mediated exclusively by the facilitative glucose transporter protein type 1 (GLUT-1) (Lund-Andersen, 1979;Pardridge et al, 1990;Klepper and Voit, 2002). Important to note is the fact that despite such facilitative transport mechanism, the actual concentration of glucose in brain is lower than it is in structures lacking a barrier, e.g.…”

Section: Glucose Transportmentioning

confidence: 99%

Energy Metabolism in Huntington’s Disease

Ribeiro¹,

Dobránsky²,

Gervásio-Carvalho³

et al. 2012

Huntington's Disease - Core Concepts and Current Advances

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Facilitated glucose transporter protein type 1 (GLUT1) deficiency syndrome: impaired glucose transport into brain – a review

Abstract: this treatable condition should be suspected in children with unexplained neurological disorders associated with epilepsy and developmental delay and confirmed by a lumbar puncture.

Cited by 161 publications

References 75 publications

Mammalian glucose permease GLUT1 facilitates transport of arsenic trioxide and methylarsonous acid

Mammalian glucose permease GLUT1 facilitates transport of arsenic trioxide and methylarsonous acid

Molecular analysis and anticonvulsant therapy in two patients with glucose transporter 1 deficiency syndrome: A successful use of zonisamide for controlling the seizures

Energy Metabolism in Huntington’s Disease

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