Chronic insulin hypoglycemia induces GLUT-3 protein in rat brain neurons.
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 about 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 with approximately 25 U/kg ultralente insulin daily at 1700 for 8 days to maintain hypoglycemia. Vascular-free and microvessel membrane fractions from brain were prepared for immunoblot analysis of GLUT-1 and GLUT-3 by use of isoform-specific antisera. 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 GLUT-3 protein expression (175.6% of control; P < 0.05). Microvascular GLUT-1 (55 kDa) tended to increase (195.6% of controls; P = 0.08) variably, whereas nonvascular GLUT-1 (45 kDa) was unchanged. We conclude that neuronal glucose transport protein (GLUT-3) expression adapts to chronic hypoglycemia. This adaptation may spare neuronal energy metabolism but could dampen neuronal signaling of glucose deprivation.
Uehara
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Y
Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland 97201, USA.
Nipper
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McCall
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D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D051274:Glucose Transporter Type 3; D007003:Hypoglycemia / Q000139:chemically induced* / Q000378:metabolism*; D007328:Insulin; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D051274:Glucose Transporter Type 3; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; C495690:Slc2a3 protein, rat