Molecular and Cellular Biochemistry

, Volume 451, Issue 1–2, pp 91–106 | Cite as

Insulin-dependent, glucose transporter 1 mediated glucose uptake and tube formation in the human placental first trimester trophoblast cells

  • Sanjay BasakEmail author
  • Srinivas Vilasagaram
  • Kishore Naidu
  • Asim K. Duttaroy


During early gestation, hypoxic condition is critically maintained by optimal glucose metabolism and transporter activities. Glucose is readily available energy nutrient required for placentation. However, limited data are available on glucose uptake and its transporters during first trimester placentation processes. To this end, effects of glucose and the roles of glucose transporters (GLUTs) were investigated during hypoxia on trophoblast migration and placental angiogenesis processes using early gestation-derived trophoblast cells, HTR8/SVneo, and first trimester human placental explant tissues. Exogenously added glucose (25 mM) significantly increased tube formation (in vitro angiogenesis) in HTR8/SVneo cells with concomitant activation of AKT-PI3K pathway and increased expression of vascular cell adhesion molecule 1 (VCAM1) compared with those in the presence of 11 mM glucose. Cobalt chloride (CoCl2)-induced hypoxia also significantly increased glucose uptake and GLUT1 expression along with tube formation and migration of HTR8/SVneo cells. During hypoxia, addition of glucose further stimulated HIF1α expression than by hypoxia alone. Cytochalasin B (cyt-B) inhibited the glucose uptake both in the presence of 11 mM and 25 mM glucose. Insulin (1 ng/ml) stimulated GLUT1 expression and tube formation and up-regulated the expression of VEGFR2 in HTR8/SVneo cells. Insulin and glucose-stimulated tube formation was inhibited by cyt-B but had no effect on hypoxia-induced tube formation. Silencing of GLUT1 inhibited the glucose and insulin-stimulated tube formation as well as glucose uptake. However, fatty acid-stimulated tube formation was not affected in GLUT1 knockdown cells. All these data suggest that glucose uptake, glucose-stimulated tube formation, and insulin-stimulated glucose uptake of the first trimester trophoblast cells, HTR8/SVneo, are mediated in part via GLUT1.


GLUT1 siRNA Cytochalasin B Glucose uptake First trimester placenta Trophoblast Insulin 



This collaborative work was initiated and started at the University of Oslo, Norway while SB worked as a visiting scientist (Boyscast Fellowship).V.S was supported by the fellowship of Council of Scientific & Industrial Research (CSIR), India. This study was supported by a grant (BT/PR6946/MED/97/89/2012) received from the Department of Biotechnology, Government of India.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interests to disclose.

Supplementary material

11010_2018_3396_MOESM1_ESM.docx (19 kb)
Supplementary material 1 (DOCX 18 KB)
11010_2018_3396_MOESM2_ESM.tif (28 mb)
Supplementary Fig. 1 Expression of angiogenic growth factors in response to glucose pre-stimulation of HTR8/SVneo cells. Cells were pre-stimulated with glucose (5.5mM, 11mM and 25mM) for 24h. mRNA expression of each gene was analyzed using quantitative real-time RT-PCR and normalized the expression to the endogenous control TBP. Fold change of expression was calculated according to the ΔΔCt method. Data are presented as fold expression of control (mean± SEM, n=9) those were analyzed by Student’s t test, * p<0.05. Supplementary material 2 (TIF 28711 KB)


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Authors and Affiliations

  1. 1.Molecular Biology Division, National Institute of NutritionIndian Council of Medical ResearchHyderabadIndia
  2. 2.Department of Nutrition, Institute of Basic Medical Sciences, Faculty of MedicineUniversity of OsloOsloNorway

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