GLUCOSE-TRANSPORTER GENE-EXPRESSION IN RAT CONCEPTUS DURING EARLY ORGANOGENESIS AND EXPOSURE TO INSULIN-INDUCED HYPOGLYCEMIC SERUM

We investigated the glucose transporter gene and protein expression du ring early organogenesis in the rat and in rat embryos cultured with h ypoglycemic serum. Erythrocyte-type glucose transporter (GLUT-1) mRNA was expressed at a high level in embryos; peak levels were reached at days 10.5-11.5 and decreased as gestational age increased. In contrast , the insulin regulatable glucose transporter (GLUT-4) mRNA was not de tected. The levels of GLUT-1 protein determined by Western blot analys is increased in parallel with expression of the glucose transporter (G LUT-1) gene and peak levels were observed on days 10.5 and 14.5, which correspond to the main periods of neural tube formation. Immunohistoc hemical staining of the embryo on day 10.5 showed that GLUT-1 protein was abundantly located in the tissue of neural tube. When embryos were cultured from day 9.5 to day 10.5 with insulin-induced hypoglycemic s erum containing 2-3 mM glucose an increased frequency of anterior neur al tube defects was observed in association with a significant reducti on of the glycolytic flux. Increased levels of GLUT-1 mRNA and protein were not observed during the culture with hypoglycemic serum compared with the levels in embryos cultured in normal serum. Addition of insu lin to normal serum (500 muU/ml) did not affect the GLUT-1 mRNA and pr otein levels. GLUT-1 mRNA and protein are strongly expressed in the em bryo during early organogenesis, especially in the tissues of the neur al tube, and the expression of the glucose transporter did not increas e in response to prolonged glycopenia. This may account for the vulner ability of embryogenesis to hypoglycemia during these critical develop mental periods.