The effects of severe maternal diabetes on glucose transport in the fetal rat.
We mimicked the condition of severe maternal diabetes by administering high doses of streptozotocin (STZ) to the pregnant rat to determine the effects of increased glucose availability on fetal glucose transport and to assess whether a relationship might exist between glucose transport and altered fetal growth. Fetuses of STZ-treated pregnant rats were growth retarded (3.86 +/- 0.13 vs. 5.29 +/- 0.06 g), hyperglycemic (30.0 +/- 1.0 vs. 5.5 +/- 0.5 mM/liter), and hyperinsulinemic (1263.8 +/- 138.3 vs. 817.9 +/- 116.7 pM/liter). Glucose uptake, Glut 1 messenger RNA (mRNA), and Glut 1 protein were greater in STZ-treated fetal brain than in controls (50%, 83%, and 50%, respectively; P < 0.05). Glut 3 mRNA levels in STZ-treated and control fetal brain were equivalent and significantly less than levels of Glut 1. Glucose uptake in muscle of STZ fetuses was 70% greater than control values (P < 0.05). Glut 1 mRNA levels were increased by 93% in STZ fetal muscle (P < 0.05). Neither Glut 3 nor Glut 4 mRNA could be detected in STZ-treated and control fetal muscle. Glut 1 protein levels were increased by 70% in STZ-treated fetal muscle compared to control muscle (P < 0.05). These observations indicate that altered glucose transport per se does not directly contribute to fetal growth retardation with maternal STZ diabetes. Perturbations in other physiological and metabolic factors may contribute to the pathogenesis of fetal growth retardation in STZ-induced diabetes during pregnancy.
Atkins
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Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois.
Flozak
A S
AS
Ogata
E S
ES
Simmons
R A
RA
D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000196:embryology; D003847:Deoxyglucose / Q000493:pharmacokinetics; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005314:Embryonic and Fetal Development; D005260:Female; D005333:Fetus / Q000378:metabolism* / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D009132:Muscles / Q000196:embryology; D011247:Pregnancy; D011254:Pregnancy in Diabetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; D003847:Deoxyglucose; D005947:Glucose