Insulin Stimulates GLUT4 Trafficking to the Syncytiotrophoblast Basal Plasma Membrane in the Human Placenta

We propose that maternal insulin stimulates placental glucose transport by promoting GLUT4 trafficking to the BM, which may enhance glucose transfer to the fetus in response to postprandial hyperinsulinemia in women with normal BMI.

The objectives of this study were to (i) determine the expression of the insulin-sensitive GLUT4 glucose transporter and IR in the syncytiotrophoblast plasma membranes across gestation in normal pregnancy and in pregnancies complicated by maternal obesity, and (ii) assess the effect of insulin on GLUT4 plasma membrane trafficking in human placental explants. Design, setting, and participants: Placental tissue was collected across gestation from women with normal body mass index (BMI) and mothers with obesity with appropriate for gestational age and macrosomic infants. MVM and BM were isolated. Main outcome measures: Protein expression of GLUT4, GLUT1, and IR were determined by western blot.

GLUT4 was exclusively expressed in the BM, and IR was predominantly expressed in the MVM, with increasing expression across gestation. BM GLUT1 expression was increased and BM GLUT4 expression was decreased in women with obesity delivering macrosomic babies. In placental villous explants, incubation with insulin stimulated Akt (S473) phosphorylation (+76%, P = 0.0003, n = 13) independent of maternal BMI and increased BM GLUT4 protein expression (+77%, P = 0.0013, n = 7) in placentas from lean women but not women with obesity.