Chronic insulin hypoglycemia induces glut3 protein in rat brain
neurons.
Uehara, Yutaka, Valerie Nipper and Anthony L. McCall, .
Departments of Cell & Developmental Biology1, Medicine2 and
Neurology3, Oregon Health Sciences University, Diabetes Program &
Research Service, Department of Veterans Affairs4 Medical Center,
Portland, OR
APStracts 4:0002E, 1997.
Near-normal glycemiaABSTRACT Near-normalization of glycemia reduces
the risks of chronic diabetic complications, but increases the risk
of serious hypoglycemia. Hypoglycemia can impair neuronal function in
the brain and diminish awareness of subsequent hypoglycemic episodes,
yet little is known of how neurons adapt to hypoglycemia. This study
tests the hypothesis that isoform-specific alterations in brain
glucose transport proteins occur in response to chronic hypoglycemia.
To study this, groups of rats were injected at 17:00h with 25U/kg
ultralente insulin to maintain hypoglycemia for 8 days. Vascular-free
and microvessel membrane fractions from brain were prepared for
immunoblot analysis of GLUT1 and GLUT3 using isoform-specific
specificantisera. Insulin treatment reduced blood glucose levels from
4.0 + 0.1 (vehicle injected controls) to 1.7 + 0.1 mmol/L on day 8.
(p< 0.001) and increased GLUT3 protein expression (175.6% of
control; p< 0.05). Microvascular GLUT1 (55 kDa) tended to
increase (195.6% of controls; p = 0.08) variably, while non-vascular
GLUT1 (45 kDa) was unchanged. We conclude that neuronal glucose
transport protein (GLUT3) expression adapts to chronic hypoglycemia.
This adaptation may spare neuronal energy metabolism, but could
dampen neuronal signaling of glucose deprivation.
Received 5 September 1996; accepted in final form 9 December
1996.
APS Manuscript Number E442-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 21 January 1997