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Expression of the electrogenic Na+–HCO3 −-cotransporters NBCe1-A and NBCe1-B in rat pancreatic islet cells

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Abstract

It was recently proposed that, in rat pancreatic islets, the production of bicarbonate accounts for the major fraction of the carbon dioxide generated by the oxidative catabolism of nutrient insulin secretagogues. In search of the mechanism(s) supporting the membrane transport of bicarbonate, the possible role of the electrogenic Na+–HCO3 −-cotransporters NBCe1-A and NBCe1-B in rat pancreatic islet cells was investigated. Expression of NBCe1-A and NBCe1-B in rat pancreatic islet cells was documented by RT-PCR, western blotting, and immunocytochemistry. The latter procedure suggested a preferential localization of NBCe1-B in insulin-producing cells. Tenidap (3–100 μM), previously proposed as an inhibitor of NBCe1-A-mediated cotransport in proximal tubule kidney cells, caused a concentration-related inhibition of glucose-stimulated insulin secretion. It also inhibited 2-ketoisocaproate-induced insulin release and to a relatively lesser extent, the secretory response to l-leucine. Tenidap (50–100 μM) also inhibited the metabolism of d-glucose in isolated islets, increased 22Na net uptake by dispersed islet cells, lowered intracellular pH and provoked hyperpolarization of plasma membrane in insulin-producing cells. This study thus reveals the expression of the electrogenic Na+–HCO3 −-cotransporters NBCe1-A and NBCe1-B in rat pancreatic islet cells, and is consistent with the participation of such transporters in the process of nutrient-stimulated insulin secretion.

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Acknowledgments

We thank Y. Zhang, E. Hupkens, and C. Demesmaeker for scientific, technical, and secretarial help. This work was supported by grants from the Belgian Foundation for Scientific Medical Research (3.4520.07) and the Deutsche Forschungsgemeinschaft (F.T). M.S.S is recipient of a scholarship from the Erasme Foundation.

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Authors and Affiliations

  1. Laboratory of Biological Chemistry and Nutrition, Université Libre de Bruxelles, Brussels, Belgium

    Muhammad S. Soyfoo, Myrna Virreira, Jason Perret & Christine Delporte

  2. Laboratory of Experimental Hormonology, Université Libre de Bruxelles, 808 Route de Lennik, 1070, Brussels, Belgium

    Nurdan Bulur, Karim Louchami, Pascale Lybaert, Willy J. Malaisse & Abdullah Sener

  3. Laboratory of Cellular and Molecular Physiology, Université Libre de Bruxelles, Brussels, Belgium

    Myrna Virreira, Raphael Crutzen & Renaud Beauwens

  4. Institute for Anatomy and Cell Biology II, Department for Molecular Embryology, University of Freiburg, Freiburg, Germany

    Eleni Roussa

  5. Institute for Physiology and Pathophysiology, Medical Faculty, University of Witten/Herdecke, Witten, Germany

    Frank Thevenod

  6. Departments of Clinical Biochemistry and Medicine, University of Manchester, Manchester, UK

    Len Best & Allen P. Yates

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  1. Muhammad S. Soyfoo
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  2. Nurdan Bulur
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  7. Jason Perret
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  8. Christine Delporte
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  9. Eleni Roussa
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  11. Len Best
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  12. Allen P. Yates
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  13. Willy J. Malaisse
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  14. Abdullah Sener
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  15. Renaud Beauwens
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Correspondence to Willy J. Malaisse.

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Soyfoo, M.S., Bulur, N., Virreira, M. et al. Expression of the electrogenic Na+–HCO3 −-cotransporters NBCe1-A and NBCe1-B in rat pancreatic islet cells. Endocr 35, 449–458 (2009). https://doi.org/10.1007/s12020-009-9175-1

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  • DOI: https://doi.org/10.1007/s12020-009-9175-1

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