Glucose utilization and glucose transporter proteins GLUT-1 and GLUT-3 in brains of diabetic (db/db) mice.
This study describes the effects of diabetes on brain growth, cerebral glucose utilization (CGU), and the glucose transporter proteins GLUT-1 and GLUT-3 in the genetically diabetic db/db mouse. Mice were studied at 5 and 10 wk of age and compared with age-matched nondiabetic littermates. At 5 wk, db/db mice were not yet hyperglycemic, but their body weights were 27.5% greater than those of their nondiabetic littermates. By 10 wk, db/db mice were both hyperglycemic (blood glucose values of 39.3 +/- 4.3 vs. 12.1 +/- 2.1 mmol/l for db/db and control, respectively) and obese, with a twofold increase in body weight. Significant reductions in brain weight were observed at 5 wk (15% decrease in brain wet wt), and no further brain growth was observed, such that by 10 wk, brains of db/db mice were 25% smaller than those of control mice; brain wet weight-to-dry weight ratios were slightly reduced. Global rates of CGU, as determined with 2-[14C]deoxyglucose, were significantly reduced in the 10-wk diabetic mice. Levels of brain glucose and brain-to-blood glucose ratios were increased in 5- and 10-wk db/db mice, reflecting adequate glucose delivery to the brain. Blood-brain barrier GLUT-1 levels were unchanged, and mRNA levels were regionally increased. The expression of the neuronal glucose transporter GLUT-3 was not reduced to a significant extent in brains of db/db mice. The results of this study indicate that the db/db mouse has markedly decelerated brain growth accompanied by global reductions in glucose metabolism that are not due to reductions in glucose transport capacity.
Vannucci
S J
SJ
Department of Pediatrics, Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, USA.
Gibbs
E M
EM
Simpson
I A
IA
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger / Q000378:metabolism
D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C495678:Slc2a1 protein, mouse; C495689:Slc2a3 protein, mouse; D005947:Glucose