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

Glucose constitutes the 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 is associated with the GLUT1 deficiency syndrome (GLUT1DS), yet none of the current in vitro models of the human BBB maybe suited for modelling such disorder. In this study, we investigated the expression of glucose transporters and glucose diffusion across the human BBB using 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. BMECs monolayers showed expression of several glucose transporters, in particular GLUT1, GLUT3 and GLUT4. Diffusion of glucose across the monolayers were 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 demonstrate the feasibility of modelling glucose across the BBB using patient-derived stem cells.