GLUCOSE TRANSPORT IN MAMMALIAN BRAIN

Project: Research project

Description

This study represents a major new direction in my laboratory to
investigate the regulatory mechanisms involved in the transport of glucose
in mammalian brain. Two glucose transporter isoforms, GLUT1 and GLUT3,
have been identified in brain. In whole brain GLUT1 is detected as two
molecular weight forms: a 55kDa form which is concentrated in the
endothelial cells of the blood-brain barrier and a 45 kDa form present in
vascular-free cortical membranes, as well as in primary cultures of
neurons and glia. In the rat, GLUT3 is expressed exclusively in the brain
but is notably absent from the blood-brain barrier of both rat and human.
Ontogeny studies indicate that in the rat brain, the concentration of
GLUT3 and both forms of GLUT1 progressively increase from the fetus
through 30 days postnatally. We have detected GLUT3 in adult rat brain in
all regions except the adenohypophysis and pineal gland, in primary
neuronal but not astrocytic cultures, and in cultured cells of neuronal
origin, e.g. PC12 and NG108-15 cells. Studies with primary cultures
revealed an increase in the GLUT 1 and 3 mRNA and protein levels which
peaked at 4 and 6 days respectively, coincident with maximal glucose
transport capacity and complete cellular differentiation. Quantitative
studies using either a specific [3H]-bis-mannose photolabel or [35S]
methionine incorporation indicated that the concentration of GLUT3 is five
times greater than GLUT1 in these cultured neurons. In serum-free
cultures GLUT1 and GLUT3 expression appears to be unaffected by ambient
glucose concentrations but is reduced by lowering the potassium
concentrations.
StatusNot started

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Facilitative Glucose Transport Proteins
Glucose
Brain
Glucose Transporter Type 1
Blood-Brain Barrier
Messenger RNA
Middle Cerebral Artery Infarction
Hippocampus
Acids
Neurons
Lactic Acid
Ketone Bodies
Glucose Transporter Type 4
Hypoglycemia
Microvessels
Hyperglycemia
In Situ Hybridization
Glucose Transporter Type 3
Cerebellum
Thalamus