GLUCOSE TRANSPORT IN MAMMALIAN BRAIN

Project: Research project

Project Details

Description

Three distinct glucose transporter isoforms have been detected in
mammalian brain. A 55kDa GLUT1 isoform is the primary transporter in the
blood-brain barrier. A lower molecular weight GLUT1 (45kDa) has been
observed in vessel-free cortex and is presumably of neuronal and or glial
origin. We have previously shown that GLUT3 is present in primary
neuronal cultures and more recently in situ hybridization studies have
confirmed its presence in neurons in intact tissue. Most recently, we, in
collaboration with Dr. Peter Davies, have detected GLUT5
immunohistochemically in human microglia and also in human monocytes
following their differentiation into tissue macrophages.

One of the major objectives of our studies has been to investigate what
effects diabetes has on the region-specific expression of these glucose
transporters in brain. We have employed two animal models of diabetes: l)
the streptozotocin-treated rat and, 2) in conjunction with Dr. Robert
Sherwin at Yale University, the BB-Wistar rat. In the first model we
found a diabetes-induced increase (20%) in the level of GLUT3 protein in
the neurohypophysis which was detected by day 3 following administration
of streptozotocin and persisted through four weeks. Conversely,GLUT1 was
decreased by 20% by day 3 and was 53% of the control level at 4 weeks.This
represents the first demonstration of stress-related regulation of GLUT3
expression.

In the BB-Wistar rats we studied the effects of diabetes and episodic
hypoglycemia on region-specific glucose transporter expression. In the
diabetic animals the levels of GLUT1 were increased 18-63% in temporal
cortex, frontal cortex, hippocampus and brain stem and decreased in
cerebellum (10%) and pineal (40%). GLUT3 was found to be increased (18-
38%) in hippocampus, brain stem and neurohypophysis. However, recurrent
hypoglycemia had no effect on the expression of either GLUT1 of GLUT3 in
either control or diabetic animals. Thus, in contrast to peripheral
tissues where there is a down-regulation of transporters associated with
diabetes, in brain an up-regulation is observed.
StatusNot started

Funding

  • NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
  • NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
  • NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
  • NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
  • NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

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