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

Caille Choffat, Dorothée
Charpentier, Eric
Diaferia, Giuseppe R.
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Published in Human molecular genetics. 2009, vol. 18, no. 3, p. 428-39
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/metabolismCells, CulturedConnexins/genetics/metabolismDiabetes Mellitus, Type 2/genetics/metabolismGap Junctions/genetics/metabolismGene ExpressionHumansInsulin/genetics/metabolismInsulin-Secreting Cells/metabolismIslets of Langerhans/metabolismPancreas/metabolismProtein Isoforms/genetics/metabolism
Stable URL https://archive-ouverte.unige.ch/unige:1263
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Other version: http://hmg.oxfordjournals.org/cgi/content/full/18/3/428
PMID: 19000992
Research groups Chirurgie viscérale (104)
Couplage cellulaire et connexines (136)
Cultures cellulaires et transplantations (519)
La transplantation d'îlots de Langerhans (623)

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Deposited on : 2009-03-31

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