Glucose utilization by the mouse brain: influence of age and diabetes

The effects of diabetes on the age-related changes in glucose utilization by various brain regions were examined in genetically diabetic (db/db) and normal (+/?) C57BL/KsJ mice following a 10 muCi injection of [3H]2-deoxyglucose (2-DOG). Brains were collected from 2 to 16-week-old mice at 30 min postinjection with 2-DOG, and the brain regions isolated by microdissection. Glucose utilization was expressed as mumol/mg/30 min for each brain region from match-paired control +/? and db/db mice. No differences in utilization were seen in brain regions from control and db/db mice at 2 weeks of age. In contrast, the diabetic condition effectively depressed the age-related increase in glucose metabolism associated with maturation in control mice between 4 and 16 weeks of age. Of particular interest was the observation that the pituitary gland of the db/db mice did not demonstrate a maturation-associated increase in glucose utilization typical of +/? mice. By 16 weeks of age, all of the brain regions of db/db mice exhibited a depressed glucose utilization rate as compared with +/? mice. These studies demonstrate that the diabetic condition impairs the normal age-related increase in CNS glucose utilization in the mouse, and suggests that decreased glucose utilization may be causally related to diabetes-associated, CNS and peripheral neuropathy.