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

Abstract

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 immunoblotting, 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.

Molecular pathways disrupted by gestational diabetes mellitus

“…GDM is associated with altered placental glucose metabolism (Osmond et al 2001, Jansson & Powell 2006 and altered amino acid transport (Jansson et al 2002) and lipid (Segura et al 2017) concentrations. Consequentially, GDM trophoblasts exhibit a two-fold increase in GLUT-1 expression and 40% increase in glucose uptake in the trophoblast basal membrane (Gaither et al 1999). These observed changes in GLUT-1 expression may potentially increase glucose uptake from the maternal circulation into the basal membrane.…”

Nutrition and Metabolic Adaptations in Physiological and Complicated Pregnancy: Focus on Obesity and Gestational Diabetes

“…Glucose transport capacity seems to be increased in GDM placentas, but with conflicting results about GLUT1 expression and activity in MVM and BM (24). At the same time, it has been demonstrated that women with Type 1 Diabetes (T1D) and first trimester hyperglycemia, showed higher expression of GLUT1 in the BM compared to healthy pregnancies (27).…”

Maternal diet modulates placental nutrient transporter gene expression in a mouse model of diabetic pregnancy

“…Contrasting findings in the literature could be related to mouse strain or timepoint of investigation, as well as mode and severity of diabetes. In human pregnancies with pre-gestational diabetes, SLC2A1/GLUT1 expression was found increased in term placenta [27], specifically in basal membrane preparations [28, 29]; however, the much longer pregnancy in human precludes a direct comparison to rodent pregnancies. Overall, our finding of increased placental Slc2a1/Glut1 expression over time in mouse placenta conforms to previous reports for human placental SLC2A1/GLUT1 expression [30], for sheep pregnancy [31, 32] and for rat [24] and mouse [33, 34].…”