title: Brain glucose transporter (Glut3) haploinsufficiency does not impair mouse brain glucose uptake.
abstract: Mouse brain expresses three principal glucose transporters. Glut1 is an endothelial marker and is the principal glucose transporter of the blood-brain barrier. Glut3 and Glut6 are expressed in glial cells and neural cells. A mouse line with a null allele for Glut3 has been developed. The Glut3(-/-) genotype is intrauterine lethal by 7days post-coitis, but the heterozygous (Glut3(+/-)) littermate survives, exhibiting rapid post-natal weight gain, but no seizures or other behavioral aberrations. At 12weeks of age, brain uptake of tail vein-injected ((3))H-2-deoxy glucose in Glut3(+/-) mice was not different from Glut3(+/+) littermates, despite 50% less Glut3 protein expression in the brain. The brain uptake of injected ((18))F-2-fluoro-2-deoxy glucose was similarly not different from Glut3(+/-) littermates in the total amount, time course, or brain imaging in the Glut3(+/-) mice. Glut1 and Glut6 protein expressions evaluated by immunoblots were not affected by the diminished Glut3 expression in the Glut3(+/-) mice. We conclude that a 50% decrease in Glut3 is not limiting for the uptake of glucose into the mouse brain, since Glut3 haploinsufficiency does not impair brain glucose uptake or utilization.
authors.affiliation: East Tennessee State University Quillen College of Medicine, Johnson City, TN, USA. stuartc@etsu.edu
authors.forename: Charles A
authors.initials: CA
authors.lastname: Stuart
authors.forename: Ian R
authors.initials: IR
authors.lastname: Ross
authors.forename: Mary E A
authors.initials: ME
authors.lastname: Howell
authors.forename: Melanie P
authors.initials: MP
authors.lastname: McCurry
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Wood
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Ceci
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kennel
authors.forename: Jonathan
authors.initials: J
authors.lastname: Wall
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000235:genetics; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005508:Food Deprivation / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D049268:Positron-Emission Tomography / Q000379:methods; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014316:Tritium / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; C495678:Slc2a1 protein, mouse; C495689:Slc2a3 protein, mouse; D019788:Fluorodeoxyglucose F18; D014316:Tritium; D003847:Deoxyglucose; D005947:Glucose