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Characterization and Modulation of Glucose Uptake in a Human Blood–Brain Barrier Model

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Abstract

The blood–brain barrier (BBB) plays a key role in limiting and regulating glucose access to glial and neuronal cells. In this work glucose uptake on a human BBB cell model (the hCMEC/D3 cell line) was characterized. The influence of some hormones and diet components on glucose uptake was also studied. 3H-2-deoxy-d-glucose ([3H]-DG) uptake for hCMEC/D3 cells was evaluated in the presence or absence of tested compounds. [3H]-DG uptake was sodium- and energy-independent. [3H]-DG uptake was regulated by Ca2+ and calmodulin but not by MAPK kinase pathways. PKC, PKA and protein tyrosine kinase also seem to be involved in glucose uptake modulation. Progesterone and estrone were found to decrease 3H-DG uptake. Catechin and epicatechin did not have any effect, but their methylated metabolites increased [3H]-DG uptake. Quercetin and myricetin decreased [3H]-DG uptake, and glucuronic acid-conjugated quercetin did not have any effect. These cells expressed GLUT1, GLUT3 and SGLT1 mRNA.

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Acknowledgments

This work was supported by the Fundação para a Ciência e Tecnologia–Fundo Social Europeu, Programa Operacional Potencial Humano da EU (PTDC/AGR-TEC/2227/2012, SFRH/BPD/75294/2010, SFRH/BD/78367/2011), and the GIP-USAL is financially supported by the Spanish Ministerio de Ciencia e Innovacion through project AGL2009-12001 and the Consolider-Ingenio 2010 Programme (CSD2007-00063). The authors thank Dr. Pierre-Olivier Couraud (INSERM U.567, Université René Descartes, Paris, France) for the hCMEC/D3 cell line.

Conflicts of interest

The authors declare there are no financial or commercial conflicts of interest.

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Authors and Affiliations

  1. Department of Biochemistry (U38.FCT), Faculty of Medicine, University of Porto, Al. Prof. Hernâni Monteiro, 4200-319, Porto, Portugal

    Manuela Meireles, Fátima Martel, João Araújo, Conceição Calhau & Ana Faria

  2. Grupo de Investigación en Polifenoles (GIP-USAL), Universidad de Salamanca, 37007, Salamanca, Spain

    Celestino Santos-Buelga, Susana Gonzalez-Manzano, Montserrat Dueñas & Ana Faria

  3. Chemistry Investigation Center (CIQ), Faculty of Sciences, University of Porto, 4169-007, Porto, Portugal

    Victor de Freitas & Nuno Mateus

  4. CINTESIS—Center for Research in Health Technologies and Information Systems, University of Porto, 4200-319, Porto, Portugal

    Conceição Calhau

  5. Faculty of Nutrition and Food Sciences, University of Porto, 4200-465, Porto, Portugal

    Ana Faria

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  1. Manuela Meireles
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Correspondence to Ana Faria.

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Meireles, M., Martel, F., Araújo, J. et al. Characterization and Modulation of Glucose Uptake in a Human Blood–Brain Barrier Model. J Membrane Biol 246, 669–677 (2013). https://doi.org/10.1007/s00232-013-9583-2

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  • DOI: https://doi.org/10.1007/s00232-013-9583-2

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