Glucose uptake is regulated by VIP through mTOR-mediated pathways in trophoblast cells

DANIEL PAPARINI; ROSANNA RAMHORST; DAIANA VOTA; VANESA HAUK; LUCILA GALLINO; CLAUDIA PÉREZ LEIRÓS; FÁTIMA MERECH; GUILLERMINA CALO; JAMES WASCHEK

Buenos aires

Congreso; LXII REUNIÓN DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA; 2017

Sociedad Argentina de Investigación Clínica

Adequate trophoblast (Tb) metabolism is crucial to allow nutrients transport from the mother to the fetus required for fetal growth and development. A dysregulation of this process may cause inappropriate fetal growth inducing Intrauterine Growth Restriction among other complications. Glucose is the main energy substrate for the placenta and the fetus and its transfer depends on maternal levels, placental glucose metabolism and facilitated transport through GLUT carrier proteins. GLUT1 appears to be one of the primary transporters of the placenta and is found at both maternal and fetal-facing Tb membrane. The vasoactive intestinal peptide (VIP) is a pleiotropic neuropeptide that was shown to inhibit glucose oxidation in rat enterocytes. We have previously demonstrated that VIP is synthesized by human Tb cells having autocrine and paracrine effects on these cells and favors Tb cell migration and invasion. Objectives: to study the role of VIP in the regulation of glucose uptake in Tb cells, placenta weight and fetal growth. Methods: we used two human Tb cell lines, Swan-71/BeWo, and implantation sites of C57BL/6 WT females mated to VIP-/- or WT males. Swan-71 VIP knocking-down was carried out using a VIP siRNA. GLUT1 and mTOR expression were evaluated by qRT-PCR and glucose uptake by flow cytometry using the fluorescent analogue 2-NBDG. Results: VIP induced glucose uptake in Tb cells through mTOR activation. An increase of GLUT1 and mTOR expression in siVIP vs. scramble transfected Tb cells and a dysregulation of glucose uptake were observed. On the other hand, VIP deficient embryos at day 14,5 showed reduced weight (WTxWT vs. WTxKO, p