Glucose regulates glut 1 function and expression in fetal rat lung and muscle in vitro.
The mechanisms that regulate cellular glucose transport (glucose uptake, Glut 1 protein, and mRNA) in the fetus are not known. We attempted to define the effects of glucose availability alone in vitro on glucose transport in fetal rat lung and muscle. On day 20 of gestation (term = 21.5 days), lung and muscle tissues were harvested from normal fetal rats, minced into explants, and cultured for 24 h in standard culture medium (lung, 28 mM; muscle, 5.5 mM glucose). Explant cultures were washed and cultured for an additional 1 or 24 h in medium containing one of four concentrations of glucose: 1) glucose free, 2) low glucose, 3) high glucose, and 4) standard. Twenty-four-hour, but not 1-h, treatment of fetal lung and muscle in vitro with low concentrations of glucose increased 2-deoxyglucose uptake and Glut 1 protein and mRNA levels (P < 0.05). Culture in high glucose medium for 24 h, but not 1 h, decreased 2-deoxyglucose uptake and Glut 1 protein and mRNA levels (P < 0.05). Culture in glucose-free medium for 24 h up-regulated glucose transport in lung and down-regulated glucose transport in muscle, indicating that regulation of fetal glucose transport may be tissue specific. These findings differ from our studies of in vivo models of altered fetal growth and abnormal glucose availability. Maternal bilateral uterine artery ligation limits glucose availability to the fetus, and glucose transport is down-regulated. Low glucose in vitro has the opposite effect. Maternal diabetes increases glucose availability to the fetus, and glucose transport is up-regulated. High glucose in vitro does the opposite. We conclude that while glucose alone in vitro affects its uptake by the cell, other factors that are altered in these in vivo conditions act in concert with glucose to regulate glucose transport in the fetus.
Simmons
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RA
Department of Pediatrics, Northwestern University, Medical School, Chicago, Illinois.
Flozak
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AS
Ogata
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ES
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D003720:Densitometry; D003847:Deoxyglucose / Q000493:pharmacokinetics; D005333:Fetus / Q000378:metabolism*; D005947:Glucose / Q000502:physiology*; D051272:Glucose Transporter Type 1; D008168:Lung / Q000196:embryology / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009132:Muscles / Q000196:embryology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; D003847:Deoxyglucose; D005947:Glucose