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Regional brain glucose uptake in genetically diabetic C57BL/KsJ mice: modulation by the opiate antagonist, nalmefene
1Department of Anatomy, Cleveland Research Laboratory, Kansas City, MO 64131.
Abstract:
A novel opiate antagonist, Nalmefene (0.5 or 5.0 mg/kg/day) was tested for its ability to modulate regional brain glucose uptake rates in genetically diabetic C57BL/KsJ mice, which normally exhibit a depressed CNS carbohydrate metabolism relative to age-matched controls. Daily Nalmefene treatment had no effect on circulating blood glucose levels in either normal or diabetic mice over a 7-week test period. However, all brain regions, except the olfactory bulbs, exhibited normalized glucose uptake rates in diabetic mice relative to controls. These data suggest a role for opiate antagonists in the modulation of CNS glucose metabolism during hyperglycemic states.
Insights
Nalmefene, an opiate antagonist, normalized brain glucose metabolism in diabetic mice without affecting blood sugar. This suggests potential for opiate antagonists in managing central nervous system glucose metabolism during hyperglycemia.
Area of Science:
- Neuroscience
- Endocrinology
- Pharmacology
Background:
- Genetically diabetic mice (C57BL/KsJ) display reduced central nervous system (CNS) carbohydrate metabolism compared to controls.
- Hyperglycemic states can negatively impact brain function due to altered glucose metabolism.
Purpose of the Study:
- To investigate the effect of the novel opiate antagonist Nalmefene on regional brain glucose uptake in diabetic mice.
- To determine if Nalmefene can modulate the depressed CNS carbohydrate metabolism observed in diabetic models.
Main Methods:
- Diabetic and normal C57BL/KsJ mice were treated daily with Nalmefene (0.5 or 5.0 mg/kg/day) for 7 weeks.
- Regional brain glucose uptake rates were measured using [specific method if available, otherwise omit or generalize].
- Circulating blood glucose levels were monitored throughout the study.
Main Results:
- Nalmefene treatment did not alter blood glucose levels in either normal or diabetic mice.
- Diabetic mice treated with Nalmefene showed normalized glucose uptake rates across most brain regions.
- The olfactory bulbs were the only brain region that did not exhibit normalized glucose uptake.
Conclusions:
- Nalmefene demonstrates the ability to normalize brain glucose metabolism in a model of diabetes.
- Opiate antagonists may play a role in modulating CNS glucose metabolism, particularly in hyperglycemic conditions.
- These findings suggest a potential therapeutic avenue for Nalmefene in managing neurological complications associated with diabetes.