Brain Glucose Transporter (Glut3) Haploinsufficiency Does Not Impair Mouse Brain Glucose Uptake

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-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 18F-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