CELLULAR-TISSUE LOCALIZATION AND REGULATION OF THE GLUT-1 PROTEIN IN BOTH THE EMBRYO AND THE VISCERAL YOLK-SAC FROM NORMAL AND EXPERIMENTALDIABETIC RATS DURING THE EARLY POSTIMPLANTATION PERIOD

We investigated the tissue-specific developmental expression and local ization of GLUT-1 protein in the rat embryo and visceral yolk sec (VYS ) during the organogenic periods of normal rats. The expression of GLU T-1 protein was then compared to that of experimental diabetic rats to test whether the diabetic state would affect the regulation of the gl ucose transporter during the early postimplantation periods (9.5-14.5 days), as we have previously demonstrated that GLUT-1 protein in embry o and VYS was down-regulated in culture with hyperglycemic medium. In the embryo, GLUT-1 protein was highly expressed during the early stage s of organogenesis (between 9.5-12.5 days) and declined thereafter, wh ereas in the VYS, its strong expression was observed at the later stag es (from 12.5-14.5 days). Immunohistochemical localization of the GLUT -1 protein in the embryo during the main periods of neurulation (9.5-1 1.5 days) showed that GLUT-1 immunoreactivity was principally observed in the neuroepithelial cells of the neural tube and also noted in the primitive heart, primitive gut, otic, and optic vesicles. At 12.5 day s, GLUT-1 protein started to be expressed in the microvessels at the c ranial portions of the neural tube, although its expression in the neu roepithelial cells still remained at the caudal (tail) portions of the neural tube. In the later stages (13.5-14.5 days) after completion of neural tube formation, GLUT-1 protein immunoreactivity substantially decreased in the neuroepithelial cells and was found mainly in the mic rovessels of the brain vesicles and spinal cord, whereas it continued to be expressed in the heart and eyes. In the VYS, its immunoreactivit y was noticeably confined to the endodermal layer, which started as a simple layer and developed wave-like folds in the later stages. The le vels of GLUT-1 protein in embryo and WS from diabetic rats, determined by Western blot analysis, were not down-regulated compared to those i n control rats at the different gestational days. Likewise, comparison of GLUT-1 protein immunoreactivity of various tissues in embryo and V YS, focusing on the neural tube, also revealed no significant differen ces between the two groups. We demonstrated that GLUT-1 protein is abu ndantly expressed in embryonic tissues and VYS during the early period s of organogenesis. The lack of down-regulation and the continuous abu ndant expression of the GLUT-1 protein despite the diabetic state in e mbryo and VYS during the early postimplantation periods may increase d elivery of glucose from the VYS into various diffrentiating embryonic cells, leading to diabeties-induced congenital malformations.