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Blood-brain glucose transfer in the mouse
E M Cornford1, D Young, J W Paxton
1Southwestern Regional V.A. Epilepsy Center, Veterans Administration West Los Angeles Medical Center, CA 90073.
Neurochemical Research
|May 1, 1993
Summary
Fasting increases brain glucose uptake in mice by enhancing transport across the blood-brain barrier (BBB). This study shows improved glucose extraction and permeability-surface area product in fasted animals, indicating BBB adaptation.
Area of Science:
- Neuroscience
- Physiology
- Biochemistry
Background:
- The blood-brain barrier (BBB) tightly regulates nutrient transport into the brain.
- Glucose is the primary energy substrate for the brain, and its transport is mediated by specific transporters.
- Understanding how BBB glucose transport adapts to metabolic states like fasting is crucial for brain energy homeostasis.
Purpose of the Study:
- To investigate the effects of a 2-day fast on glucose transport across the blood-brain barrier (BBB) in mice.
- To determine if fasting alters the kinetics (Vmax and Km) of brain glucose transport.
- To confirm the identity of the glucose transporter expressed at the mouse brain capillary endothelium.
Main Methods:
- Intracarotid injection technique in anesthetized mice to measure BBB glucose transport.
- Comparison of glucose transport parameters between normally fed and 2-day fasted mice.
- Immunocytochemical analysis using an antiserum against human erythrocyte glucose transporter (GLUT-1) to identify the brain transporter.
Main Results:
- Fasting significantly reduced plasma glucose levels and forebrain weight.
- Brain glucose extraction and the unsaturated permeability-surface area product across the BBB were significantly increased in fasted mice.
- Maximal velocity (Vmax) and half-saturation constant (Km) for glucose transport did not show significant changes, suggesting a different mechanism for increased uptake.
- Immunocytochemistry confirmed the presence of GLUT-1 transporter in mouse brain capillary endothelium, with similar immunoreactivity in fed and fasted states.
Conclusions:
- A 2-day fast in mice leads to significant adaptations in BBB glucose transport, enhancing brain glucose uptake despite lower plasma glucose levels.
- The observed increase in glucose uptake is likely due to increased brain glucose extraction and enhanced permeability-surface area product, rather than changes in Vmax or Km of the GLUT-1 transporter.
- These findings highlight the brain's ability to maintain energy supply during fasting through BBB adaptations.