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

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)428-439
Number of pages12
JournalHuman Molecular Genetics
Volume18
Issue number3
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

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