Fulltext

Cx36 makes channels coupling human pancreatic β-cells, and correlates with insulin expression

Serre-Beinier, Véronique ; Bosco, Domenico ; Zulianello, Laurence ; Charollais, Anne ; Caille, Dorothée ; Charpantier, Eric ; Gauthier, Benoit R. ; Diaferia, Giuseppe R. ; Giepmans, Ben N. ; Lupi, Roberto ; Marchetti, Piero ; Deng, Shaoping ; Buhler, Léo ; Berney, Thierry ; Cirulli, Vincenzo ; Meda, Paolo

In: Human Molecular Genetics, 2009, vol. 18, no. 3, p. 428-439

Add to personal list
    Title
    • Cx36 makes channels coupling human pancreatic β-cells, and correlates with insulin expression
    Author
    • Serre-Beinier, Véronique. Surgical Research Unit, Department of Surgery
    • Bosco, Domenico. Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals, Geneva, Switzerland
    • Zulianello, Laurence. Department of Cell Physiology and Metabolism, University of Geneva School of Medicine, CMU 1, rue Michel-Servet, 1211 Geneva 4, CH, Switzerland
    • Charollais, Anne. Department of Cell Physiology and Metabolism, University of Geneva School of Medicine, CMU 1, rue Michel-Servet, 1211 Geneva 4, CH, Switzerland
    • Caille, Dorothée. Department of Cell Physiology and Metabolism, University of Geneva School of Medicine, CMU 1, rue Michel-Servet, 1211 Geneva 4, CH, Switzerland
    • Charpantier, Eric. Department of Cell Physiology and Metabolism, University of Geneva School of Medicine, CMU 1, rue Michel-Servet, 1211 Geneva 4, CH, Switzerland
    • Gauthier, Benoit R.. Department of Cell Physiology and Metabolism, University of Geneva School of Medicine, CMU 1, rue Michel-Servet, 1211 Geneva 4, CH, Switzerland
    • Diaferia, Giuseppe R.. Islet Research Laboratory, The Whittier Institute for Diabetes, University of California San Diego, La Jolla, CA, USA
    • Giepmans, Ben N.. Department of Cell Biology, University of Groningen, Groningen, The Netherlands
    • Lupi, Roberto. Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy
    • Marchetti, Piero. Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy
    • Deng, Shaoping. Department of Surgery, University of Pennsylvania, Philadelphia, PA, USA
    • Buhler, Léo. Surgical Research Unit, Department of Surgery
    • Berney, Thierry. Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals, Geneva, Switzerland
    • Cirulli, Vincenzo. Islet Research Laboratory, The Whittier Institute for Diabetes, University of California San Diego, La Jolla, CA, USA
    • Meda, Paolo. Department of Cell Physiology and Metabolism, University of Geneva School of Medicine, CMU 1, rue Michel-Servet, 1211 Geneva 4, CH, Switzerland
    Document Type
    • Postprint
    Language
    • English
    Published in
    • Human Molecular Genetics, 2009, vol. 18, no. 3, p. 428-439. Oxford University Press
    Other Version
    Classification
    • Health
    OAI-PMH Identifier
    • oai:doc.rero.ch:296666
    Summary
    Previous studies have documented that the insulin-producing β-cells of laboratory rodents are coupled by gap junction channels made solely of the connexin36 (Cx36) protein, and have shown that loss of this protein desynchronizes β-cells, leading to secretory defects reminiscent of those observed in type 2 diabetes. Since human islets differ in several respects from those of laboratory rodents, we have now screened human pancreas, and islets isolated thereof, for expression of a variety of connexin genes, tested whether the cognate proteins form functional channels for islet cell exchanges, and assessed whether this expression changes with β-cell function in islets of control and type 2 diabetics. Here, we show that (i) different connexin isoforms are differentially distributed in the exocrine and endocrine parts of the human pancreas; (ii) human islets express at the transcript level different connexin isoforms; (iii) the membrane of β-cells harbors detectable levels of gap junctions made of Cx36; (iv) this protein is concentrated in lipid raft domains of the β-cell membrane where it forms gap junctions; (v) Cx36 channels allow for the preferential exchange of cationic molecules between human β-cells; (vi) the levels of Cx36 mRNA correlated with the expression of the insulin gene in the islets of both control and type 2 diabetics. The data show that Cx36 is a native protein of human pancreatic islets, which mediates the coupling of the insulin-producing β-cells, and contributes to control β-cell function by modulating gene expression