Brain glucose transporter (Glut3) haploinsufficiency does not impair mouse brain glucose uptake

• Published in: Brain research 2011-04, Vol.1384, p.15-22
• Main Authors: Stuart, Charles A, Ross, Ian R, Howell, Mary E.A, McCurry, Melanie P, Wood, Thomas G, Ceci, Jeffrey D, Kennel, Stephen J, Wall, Jonathan
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Biochemistry and metabolism; Biological and medical sciences; Blood Glucose - genetics; blood-brain barrier; Brain; Brain - diagnostic imaging; Brain - metabolism; Central nervous system; Deoxyglucose - metabolism; Female; Fluorodeoxyglucose F18 - pharmacokinetics; Food Deprivation - physiology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - genetics; glucose; Glucose - metabolism; Glucose Transporter Type 1 - genetics; Glucose Transporter Type 1 - metabolism; Glucose Transporter Type 3 - deficiency; Glucose Transporter Type 3 - genetics; glucose transporters; Glucose uptake; Glut1; Glut3; Glut6; heterozygosity; image analysis; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; neuroglia; Neurology; null alleles; Positron-Emission Tomography - methods; protein synthesis; seizures; tail; Tomography, Emission-Computed, Single-Photon - methods; Tritium - metabolism; Vertebrates: nervous system and sense organs; weight gain
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2011.02.014

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 7 days post-coitis, but the heterozygous (Glut3+/− ) littermate survives, exhibiting rapid post-natal weight gain, but no seizures or other behavioral aberrations. At 12 weeks of age, brain uptake of tail vein-injected3 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 injected18 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.