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 t he effects of increased glucose availability on fetal glucose transpor t and to assess whether a relationship might exist between glucose tra nsport and altered fetal growth. Fetuses of STZ-treated pregnant rats were growth retarded (3.86 +/- 0.13 vs. 5.29 +/- 0.06 g), hyperglycemi c (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 mess enger RNA (mRNA), and Glut 1 protein were greater in STZ-treated fetal brain than in controls (50%, 83%, and 50%, respectively; P < 0.05). G lut 3 mRNA levels in STZ-treated and control fetal brain were equivale nt and significantly less than levels of Glut 1. Glucose uptake in mus cle of STZ fetuses was 70% greater than control values (P < 0.05). Glu t 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 co ntrol fetal muscle. Glut 1 protein levels were increased by 70% in STZ -treated fetal muscle compared to control muscle (P < 0.05). These obs ervations indicate that altered glucose transport per se does not dire ctly contribute to fetal growth retardation with maternal STZ diabetes . Pertubations in other physiological and metabolic factors may contri bute to the pathogenesis of fetal growth retardation in STZ-induced di abetes during pregnancy.