Intra-uterine growth restriction differentially regulates perinatal brain and skeletal muscle glucose transporters.
Employing Western blot analysis, we investigated the effect of maternal uterine artery ligation causing uteroplacental insufficiency with asymmetrical intrauterine growth restriction (IUGR) upon fetal (22d) and postnatal (1d, 7d, 14d and 21d) brain (Glut 1 and Glut 3) and skeletal muscle (Glut 1 and Glut 4) glucose transporter protein concentrations. IUGR was associated with a approximately 42% decline in fetal plasma glucose (p<0.05) and a approximately 25% decrease in fetal body weights (p<0.05) with no change in brain weights when compared to the sham operated controls (SHAM). In addition, IUGR caused a approximately 45% increase in fetal brain Glut 1 (55 kDa) with no change in Glut 3 (50 kDa) protein concentrations. This fetal brain Glut 1 change persisted, though marginal, through postnatal suckling stages of development (1d-21d), with no concomitant change in brain Glut 3 levels at day 1. In contrast, in the absence of a change in fetal skeletal muscle Glut 1 levels (48 kDa), a 70% increase was observed in the 1d IUGR with no concomitant change in either fetal or postnatal Glut 4 levels (45 kDa). The change in skeletal muscle Glut 1 levels normalized by d7 of age. We conclude that IUGR with hypoglycemia led to a compensatory increase in brain and skeletal muscle Glut 1 concentrations with a change in the brain preceding that of the skeletal muscle. Since Glut 1 is the isoform of proliferating cells, fetal brain weight changes were not as pronounced as the decline in somatic weight. The increase in Glut 1 may be protective against glucose deprivation in proliferating fetal brain cells and postnatal skeletal myocytes which exhibit 'catch-up growth', thereby preserving the specialized function mediated by Glut 3 and Glut 4 towards maintaining the intracellular glucose milieu.
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Division of Neonatology, Department of Pediatrics, St. Louis University School of Medicine, The Pediatric Research Institute, Cardinal Glennon Children's Hospital, St. Louis, Missouri 63104, USA.
Das
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Tracy
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Devaskar
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D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D005314:Embryonic and Fetal Development / Q000502:physiology; D005317:Fetal Growth Retardation / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley
D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C495679:Slc2a1 protein, rat; C495690:Slc2a3 protein, rat; C495694:Slc2a4 protein, rat