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Diabetes Alters the Expression and Activity of the Human Placental GLUT1 Glucose Transporter¹

Department of Obstetrics and Gynecology, University of Medicine and Dentistry of New Jersey- New Jersey Medical School, Newark, New Jersey 07103

Address all correspondence and requests for reprints to: Nicholas P. Illsley, D.Phil., Department of Obstetrics and Gynecology, Medical Sciences Building, E506, University of Medicine and Dentistry-New Jersey Medical School, 185 South Orange Avenue, Newark, New Jersey 07103-2714. E-mail: illsleni{at}umdnj.edu

This study was designed to investigate the effects of maternal diabetes on glucose transporter expression and glucose transport activity in the human placenta. Syncytiotrophoblast microvillous and basal membranes were prepared from placental tissue obtained at term from pregestational diabetics (White class B) and gestational diabetics controlled either by diet alone (class A1) or by diet and insulin (class A2). These membranes were used to measure GLUT1 glucose transporter expression and D-glucose transport activity. Diabetic groups showed no differences in placental weights or neonatal birth weights compared to controls, although 8 of 25 diabetic fetuses were macrosomic. Glycemic control in the diabetics at term, as assessed by maternal glycosylated hemoglobin, was within normal limits. Basal membrane GLUT1 density was about 2-fold higher in all diabetic groups compared to that in controls, as measured by immuoblotting, whereas no changes were found for the microvillous membranes. D-Glucose uptake across the basal membrane was increased by 40% in the diabetic groups; no changes were observed for the microvillous membrane. These results demonstrate that diabetes causes an increase in basal membrane GLUT1 expression and activity that persists despite a lack of evidence for current or recent maternal hyperglycemia. This suggests the potential for an extended increase in transplacental glucose flux in the absence of maternal hyperglycemia, which may contribute to fetal macrosomia and the other consequences of diabetic pregnancy.

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