Effects of anticonvulsants on GLUT1-mediated glucose transport in GLUT1 deficiency syndrome in vitro.
Facilitative type-1 glucose transporter (GLUT1) deficiency syndrome is caused by a defect of glucose transport into brain, resulting in an epileptic encephalopathy. Seizures respond effectively to a ketogenic diet, but a subgroup of patients require add-on anticonvulsant therapy or do not tolerate the diet. With the exception of barbiturates, which have been shown to inhibit GLUT1 function, no anticonvulsants have been investigated for possible interactions with GLUT1. Kinetic analyses of (14)C-labeled 3-O-methyl glucose (3OMG) uptake into erythroctes were performed in 11 patients and 30 controls. For in vitro inhibition studies, zero-trans influx of 3OMG (5 mmol/L) into erythrocytes was determined following preincubation with diazepam, carbamazepine, phenytoin, and chloralhydrate. In addition, the effects of ethanol on cell lysis and 3OMG transport into erythrocytes were determined. In patients, mean 3OMG influx was 53% of controls. Ethanol, diazepam, and chloralhydrate significantly inhibited GLUT1 function. Erythrocyte cell lysis was evident at concentrations of 2.5% ethanol. Diazepam, chloralhydrate, and ethanol are inhibitors of GLUT1 function in vitro and might potentiate the effects of GLUT1-mediated glucose transport in patients with GLUT1 deficiency syndrome. In contrast, no inhibitory effects were observed for carbamazepine and phenytoin, indicating that these substances might be preferable for additional seizure control in this disorder.
Klepper
Jörg
J
Department of Pediatric Neurology, University of Essen, Hufelandstrasse 55, 45122 Essen, Germany. joerg.klepper@uni-essen.de
Flörcken
Anne
A
Fischbarg
Jorge
J
Voit
Thomas
T
D019325:3-O-Methylglucose / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology*; D001692:Biological Transport; D001812:Blood-Brain Barrier; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D051272:Glucose Transporter Type 1; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D008297:Male; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000172:deficiency*; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology; D013577:Syndrome
D000927:Anticonvulsants; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human; D019325:3-O-Methylglucose; D000431:Ethanol