Effect of maternal diabetes on the expression of genes regulating fetal brain glucose uptake.
Diabetes alters adult brain glucose uptake and glucose transporter 1 gene expression. To investigate the effect of diabetes on genes regulating fetal brain glucose uptake, we examined the effect of moderate (blood glucose 10-16.7 mM, normoinsulinemia) and severe (blood glucose > 16.8 mM, hypoinsulinemia) maternal diabetes on the expression of genes regulating fetal brain glucose uptake in the genetically nonobese diabetic mouse. In the moderately diabetic state, a 50% decline in fetal brain GLUT1 mRNA levels was associated with a 20% increase in the corresponding GLUT1 protein levels. Simultaneously, although fetal brain GLUT3 mRNA and protein levels were barely detectable, no change in hexokinase I enzyme mRNA, protein (115,000 and 100,000 M(r)) or activity, was noted. In the severe form of maternal diabetes GLUT1 protein was unchanged, GLUT3 protein levels remained low, and a 2- to 3-fold increase in the lower molecular form of the hexokinase I protein (100,000 M(r)) and enzyme activity occurred. These observations suggest that moderate and severe forms of maternal diabetes do not affect the fetal brain glucose transporter levels to a physiologically significant extent. The severe form of maternal diabetes, however, enhances 1.5- to 3-fold the expression and activity of hexokinase I. This enzyme mediates the rate-limiting step in brain glucose metabolism, namely the intracellular conversion of glucose to glucose-6-phosphate.
Department of Pediatrics, St. Louis University School of Medicine, Missouri.
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Schroeder
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Devaskar
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Trail
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Demello
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Cole
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Devaskar
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D001923:Brain Chemistry; D005260:Female; D005333:Fetus / Q000378:metabolism* / Q000502:physiology; D015870:Gene Expression / Q000235:genetics / Q000502:physiology; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics*; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D006593:Hexokinase / Q000235:genetics*; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics
D001786:Blood Glucose; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C495678:Slc2a1 protein, mouse; C495689:Slc2a3 protein, mouse; D006593:Hexokinase; D005947:Glucose