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

• Published in: Human molecular genetics Vol. 18; no. 3; p. 428
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Oxford Oxford Publishing Limited (England) 01-02-2009
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddn370

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.