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

被引:24
作者
Al-Ahmad, Abraham J. [1 ]
机构
[1] Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Dept Pharmaceut Sci, 1300 South Coulter St, Amarillo, TX 79106 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2017年 / 313卷 / 04期
关键词
blood-brain barrier; glucose; stem cells; IN-VITRO MODELS; BARRIER MODEL; DEFICIENCY SYNDROME; GLUT1; DEFICIENCY; NEURONS; LOCALIZATION; DERIVATION; ASTROCYTES; GUIDELINES; INTEGRITY;
D O I
10.1152/ajpcell.00116.2017
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:C421 / C429
页数:9
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