EFFECT OF STREPTOZOTOCIN-INDUCED MATERNAL DIABETES ON FETAL-RAT BRAINGLUCOSE TRANSPORTERS

Glucose, an essential substrate for brain oxidative metabolism, is tra nsported across the blood-brain barrier and into neuronal and glial ce lls via Glut 1 and Glut 3 facilitative glucose transporter isoforms. T o examine the effect of excessive circulating glucose on fetal brain g lucose transporter expression, we investigated the effect of streptozo tocin-induced maternal diabetes (SEVERE-D; n = 29) on the 20-d gestati on fetal rat brain Glut 1 and Glut 3. We studied the effect of strepto zotocin alone (STZ-ND; n = 12) in a nondiabetic state as well, along w ith vehicle injected controls (C; it = 24). Tn the presence of fetal h yperglycemia (12.63 +/- 0.52 nM- SEVERE-D versus 2.35 +/- 0.28-STZ-ND and 2.42 +/- 0.16-C; p < 0.001) and hypoinsulinemia (0.38 +/- 0.03 nM- SEVERE-D versus 0.50 +/- 0.07-STZ-ND and 0.55 +/- 0.06-C, p < 0.02), n o detectable change in fetal brain Glut 1 and Glut 3 pretranslational expression (transcription/elongation rates and corresponding steady st ate mRNA levels) was noted when simultaneously compared with the STZ-N D and C groups. Tn contrast, a trend toward a decline in Glut 1 (simil ar to 25 to 30%, p = 0.05) and a substantive decrease in Glut 3 (simil ar to 35 to 50%, p = 0.0006) protein concentrations was present in bot h the STZ-ND and SEVERE-D groups when compared with the C group. These observations support a chemical effect of streptozotocin independent of maternal diabetes upon the translation or posttranslational process ing of fetal brain glucose transporters. Maternal diabetes with fetal hyperglycemia, however, failed to substantively alter fetal brain gluc ose transporters independent of the streptozotocin effects upon neuroe ctodermally derived tissues, We conclude that maternal diabetes with a ssociated overt fetal hyperglycemia does not significantly change feta l brain glucose transporter levels.