Glucose utilization and the glucose transporter proteins, glut1 and glut3, in brains of diabetic, db/db, mice. Vannucci, Susan J., E. Michael Gibbs, and Ian A. Simpson. Department of Pediatrics, Milton S. Hershey Medical Center, Hershey, Pennsylvania, 17033; #Department of Metabolic Diseases, Central Research Division, Pfizer, Inc., Groton, Connecticut 06340; and Experimental Diabetes, Metabolism and Nutrition Section, Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, 20892
APStracts 3:0221E, 1996.
This study describes the effects of diabetes on brain growth, cerebral glucose utilization and the glucose transporter proteins, GLUT1 and GLUT3, in the genetically diabetic db/db mouse. Mice were studied at 5 and 10 weeks of age and compared with age-matched non-diabetic littermates. At 5 weeks db/db mice were not yet hyperglycemic but their body weights were 27.5% greater than their non-diabetic littermates. By 10 weeks db/db mice were both hyperglycemic ( blood glucose values of 39.3 + 4.3 mM/L vs. 12.1 + 2.1 mM/L, db/db and control, respectively) and obese, with a 2-fold increase in body weight. Significant reductions in brain weight were observed at 5 weeks (15% decrease in brain wet weight) and no further brain growth was observed such that by 10 weeks brains of db/db mice were 25% smaller than control; brain wet weight/dry weight ratios were unchanged. Global rates of cerebral glucose utilization (CGU), as determined with 14C-2-deoxyglucose, were significantly reduced in the 10 week diabetic mice. Levels of brain glucose and brain/blood glucose ratios were increased in 5 and 10 week db/db mice, reflecting adequate glucose delivery to the brain. Blood-brain barrier GLUT1 levels were unchanged and mRNA levels were regionally increased. The expression of the neuronal glucose transporter GLUT3 was not dramatically altered 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, suggesting that the db gene product, the leptin receptor, may regulate a neurotrophic pathway. 

Received 16 April 1996; accepted in final form 29 October 1996.
APS Manuscript Number E190-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996