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Insulin-Like Growth Factor-1 Selectively Increases Glucose Utilization in Brains of Aged Animals

Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157

Address all correspondence and requests for reprints to: William E. Sonntag, Ph.D., Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1083.

Previous studies indicate that insulin-like growth factor-1 is an important neurotrophic agent and that decreases in brain concentrations of IGF-1 and the type 1 IGF receptor have an important role in the age-related decline in memory, neuronal function and possibly dendritic architecture. In this study, we assessed the effects of age and IGF-1 replacement on local cerebral glucose utilization (LCGU). Three groups of male Brown-Norway rats (7, 18 and 28 months of age) were implanted with Alzet minipumps and either saline or IGF-1 (50ng/0.5 µl/hour) was infused into the lateral ventricle for 28 days. On day 28, LCGU was measured by infusion of 2-[¹⁴C]deoxyglucose during the dark phase of the light/dark cycle. Results indicate that glucose utilization significantly decreased with age throughout the brain including the anterior cingulate, sensorimotor and retrosplenial cortex, CA1, CA3 and dentate gyrus of hippocampus and several regions of the hypothalamus. Administration of IGF-1 to aged animals increased rates of LCGU in the anterior cingulate of the cortex (14.2%), CA1 region of the hippocampus (11.0%) and the arcuate nucleus of the hypothalamus (12.0%). Our results indicate that although glucose utilization decreases with age throughout the brain, the effects of IGF-1 infusion are manifest only in specific brain regions. Since IGF-1 has been shown to reverse the age-related decrease in memory, these results suggest that despite the wide distribution of the type 1 IGF receptor the actions of IGF-1 on glucose utilization are highly localized. Additionally, the close association between glucose utilization and excitatory amino acid activity suggests that IGF-1 may act on specific neural pathways to increase glutamate activity in brain regions associated with learning and memory.

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