Comparative study of expression and activity of glucose transporters between stem cell-derived brain microvascular endothelial cells and hCMEC/D3 cells

Am J Physiol Cell Physiol. 2017 Oct 1;313(4):C421-C429. doi: 10.1152/ajpcell.00116.2017. Epub 2017 Aug 9.


Glucose constitutes a major source of energy of mammalian brains. Glucose uptake at the blood-brain barrier (BBB) occurs through a facilitated glucose transport, through glucose transporter 1 (GLUT1), although other isoforms have been described at the BBB. Mutations in GLUT1 are associated with the GLUT1 deficiency syndrome, yet none of the current in vitro models of the human BBB maybe suited for modeling such a disorder. In this study, we investigated the expression of glucose transporters and glucose diffusion across brain microvascular endothelial cells (BMECs) derived from healthy patient-derived induced pluripotent stem cells (iPSCs). We investigated the expression of different glucose transporters at the BBB using immunocytochemistry and flow cytometry and measured glucose uptake and diffusion across BMEC monolayers obtained from two iPSC lines and from hCMEC/D3 cells. BMEC monolayers showed expression of several glucose transporters, in particular GLUT1, GLUT3, and GLUT4. Diffusion of glucose across the monolayers was mediated via a saturable transcellular mechanism and partially inhibited by pharmacological inhibitors. Taken together, our study suggests the presence of several glucose transporters isoforms at the human BBB and demonstrates the feasibility of modeling glucose across the BBB using patient-derived stem cells.

Keywords: blood-brain barrier; glucose; stem cells.

Publication types

  • Comparative Study

MeSH terms

  • Blood-Brain Barrier / cytology
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism*
  • Cell Line
  • Diffusion
  • Electric Impedance
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Glucose / metabolism*
  • Glucose Transport Proteins, Facilitative / antagonists & inhibitors
  • Glucose Transport Proteins, Facilitative / genetics
  • Glucose Transport Proteins, Facilitative / metabolism*
  • Glucose Transporter Type 1 / genetics
  • Glucose Transporter Type 1 / metabolism
  • Glucose Transporter Type 3 / genetics
  • Glucose Transporter Type 3 / metabolism
  • Glucose Transporter Type 4 / genetics
  • Glucose Transporter Type 4 / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / drug effects
  • Induced Pluripotent Stem Cells / metabolism*
  • Microvessels / cytology
  • Microvessels / drug effects
  • Microvessels / metabolism*
  • Phenotype
  • Sodium-Glucose Transporter 1 / genetics
  • Sodium-Glucose Transporter 1 / metabolism
  • Symporters / genetics
  • Symporters / metabolism


  • Glucose Transport Proteins, Facilitative
  • Glucose Transporter Type 1
  • Glucose Transporter Type 3
  • Glucose Transporter Type 4
  • SLC2A1 protein, human
  • SLC2A3 protein, human
  • SLC2A4 protein, human
  • SLC5A3 protein, mouse
  • Slc5a1 protein, mouse
  • Sodium-Glucose Transporter 1
  • Symporters
  • Glucose