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Scientific article
English

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

Contributors

Serre Beinier, Véronique; Bosco, Domenico; Zulianello, Laurence; Charollais, Anne; Caille Choffat, Dorothée; Charpentier, Eric; Gauthier, Benoît; Diaferia, Giuseppe R.; Giepmans, Ben N.; Lupi, Roberto; Marchetti, Piero; Deng, Shaoping; Buehler, Leo Hans; Berney, Thierry; Cirulli, Vincenzo; Meda, Paolo

Published in

Human molecular genetics, vol. 18, no. 3, p. 428-439

Publication date

2009

Abstract

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.

Keywords

  • Cell Membrane/genetics/metabolism
  • Cells, Cultured
  • Connexins/genetics/metabolism
  • Diabetes Mellitus, Type 2/genetics/metabolism
  • Gap Junctions/genetics/metabolism
  • Gene Expression
  • Humans
  • Insulin/genetics/metabolism
  • Insulin-Secreting Cells/metabolism
  • Islets of Langerhans/metabolism
  • Pancreas/metabolism
  • Protein Isoforms/genetics/metabolism

UNIGE affiliation entities

UNIGE research groups

Citation (ISO format)

SERRE BEINIER, Véronique et al. Cx36 makes channels coupling human pancreatic beta-cells, and correlates with insulin expression. In: Human molecular genetics, 2009, vol. 18, n° 3, p. 428–439. doi: 10.1093/hmg/ddn370

Main files (1)

Article (Accepted version)

Secondary files (1)

Supplemental data

Identifiers

Additional URL for this publication

http://hmg.oxfordjournals.org/cgi/content/full/18/3/428

Journal ISSN

0964-6906
817views
150downloads

Technical informations

Creation

31/03/2009 11:17:00

First validation

31/03/2009 11:17:00

Update

26/03/2026 10:42:07

Status update

26/03/2026 10:42:07

Last indexation

26/03/2026 10:47:17
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