Cx36 makes channels coupling human pancreatic β-cells, and correlates with insulin expression
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
In: Human Molecular Genetics, 2009, vol. 18, no. 3, p. 428-439
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- 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