Glucose, an essential substrate for brain oxidative metabolism, is transported across the blood-brain barrier and into neuronal and glial cells via Glut 1 and Glut 3 facilitative glucose transporter isoforms. To examine the effect of excessive circulating glucose on fetal brain glucose transporter expression, we investigated the effect of streptozotocin-induced maternal diabetes (SEVERE-D;n= 29) on the 20-d gestation fetal rat brain Glut 1 and Glut 3. We studied the effect of streptozotocin alone (STZ-ND;n= 12) in a nondiabetic state as well, along with vehicle injected controls (C;n= 24). In the presence of fetal hyperglycemia (12.63± 0.82 nM- SEVERE-Dversus2.35 ± 0.28-STZ-ND and 2.42± 0.16-C;p< 0.001) and hypoinsulinemia (0.38 ± 0.03 nM-SEVERE-Dversus0.50 ± 0.07-STZ-ND and 0.55 ± 0.06-C;p< 0.02), no detectable change in fetal brain Glut 1 and Glut 3 pretranslational expression (transcription/elongation rates and corresponding steady state mRNA levels) was noted when stimultaneously compared with the STZ-ND and C groups. In contrast, a trend toward a decline in Glut 1 (≈25 to 30%,p= 0.05) and a substantive decrease in Glut 3 (≈35 to 50%,p= 0.0006) protein concentrations was present in both the STZ-ND and SEVERE-D groups when compared with C group. These observations support a chemical effect of streptozotocin independent of maternal diabetes upon the translation or postranslational processing of fetal brain glucose transporters. Maternal diabetes with fetal hyperglycemia, however, failed to substantively alter fetal brain glucose transporters independent of the streptozotocin effects upon neuroectodermally derived tissues. We conclude that maternal diabetes with associated overt fetal hyperglycemia does not significantly change fetal brain glucose transporter levels.Abbreviations: Glut,glucose transporter;STZ-ND,streptozotocin-treated nondiabetic;SEVERE-D,streptozotocin-treated severely diabetic;C,vehicle control;NOD,nonobese diabetic;ANOVA,analysis of variance