Publication

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

Serre-Beinier, V., Bosco, D., Zulianello, L., Charollais, A., Caille, D., Charpantier, E., Gauthier, B. R., Diaferia, G. R., Giepmans, B. N., Lupi, R., Marchetti, P., Deng, S., Buhler, L., Berney, T., Cirulli, V. & Meda, P., 1-Feb-2009, In : Human Molecular Genetics. 18, 3, p. 428-439 12 p.

Research output: Contribution to journalArticleAcademicpeer-review

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

Previous studies have documented that the insulin-producing beta-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 beta-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 beta-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 beta-cells harbors detectable levels of gap junctions made of Cx36; (iv) this protein is concentrated in lipid raft domains of the beta-cell membrane where it forms gap junctions; (v) Cx36 channels allow for the preferential exchange of cationic molecules between human beta-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 beta-cells, and contributes to control beta-cell function by modulating gene expression.

Original languageEnglish
Pages (from-to)428-439
Number of pages12
JournalHuman Molecular Genetics
Volume18
Issue number3
Publication statusPublished - 1-Feb-2009

    Keywords

  • GAP-JUNCTION CHANNELS, B-CELLS, ISLET TRANSPLANTATION, ZONULA OCCLUDENS-1, INVIVO MODULATION, SECRETING CELLS, GENE-EXPRESSION, ION CHANNELS, MOUSE-BRAIN, CONNEXIN36

View graph of relations

ID: 4834628