Glucose transporters in the human placenta.
The availability of antibodies and cDNA probes specific for the various members of the facilitated-diffusion glucose transporter (GLUT) family has enabled researchers to obtain a much clearer picture of the mechanisms for placental uptake and transplacental transport of glucose. This review examines studies of human placental glucose transport with the aim of providing a model which describes the transporter isoforms present in the placenta, their cellular localization and functional significance. The GLUT1 glucose transporter, present on both the microvillous and basal membranes of the syncytial barrier, is the primary isoform involved in the transplacental movement of glucose. Although GLUT3 mRNA is widely distributed, GLUT3 protein is localized to the arterial component of the vascular endothelium, where it may play a role in enhancing transplacental glucose transport. This data is in contrast to the situation in other mammalian species, such as the mouse, rat and sheep, where GLUT3 protein is not only present in those epithelial cells which carry out transplacental transport but becomes an increasingly prominent isoform as gestation progresses. The asymmetric distribution of GLUT1 in the human syncytiotrophoblast (microvillous>basal) means that basal GLUT1 acts as the rate limiting step in transplacental transfer. Changes in basal GLUT1 therefore have the potential to cause alterations in transplacental transport of glucose. Although there appear to be no changes in syncytial GLUT1 expression in intrauterine growth retardation, in diabetic pregnancies increases in basal GLUT1 expression and activity have been observed, with significant consequences for the maternal-fetal flux of glucose. Little is known of glucose transporter regulation in the placenta save for the effects of hyper- and hypoglycemia. GLUT1 expression and activity appear to be inversely related to extracellular glucose concentration, however within the physiological range, GLUT1 expression is relatively refractory to glucose concentration. Information is still needed on gestational development, on the expression and activity in well-defined conditions of intrauterine growth retardation, on the mechanisms and consequences of the changes observed in diabetic pregnancy and on the role of external agents other than glucose in regulating placental glucose transport.
Illsley
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NP
Department of Obstetrics, Gynecology and Women's Health, UMD-New Jersey Medical School, Newark, NJ 07103-2714, USA. illsleni@umdnj.edu
D000818:Animals; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism; D006801:Humans; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D010929:Placentation; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013045:Species Specificity
D009004:Monosaccharide Transport Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger