TY - JOUR
T1 - Cx36 makes channels coupling human pancreatic β-cells, and correlates with insulin expression
AU - Serre-Beinier, Véronique
AU - Bosco, Domenico
AU - Zulianello, Laurence
AU - Charollais, Anne
AU - Caille, Dorothée
AU - Charpantier, Eric
AU - Gauthier, Benoit R.
AU - Diaferia, Giuseppe R.
AU - Giepmans, Ben N.
AU - Lupi, Roberto
AU - Marchetti, Piero
AU - Deng, Shaoping
AU - Buhler, Léo
AU - Berney, Thierry
AU - Cirulli, Vincenzo
AU - Meda, Paolo
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
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U2 - 10.1093/hmg/ddn370
DO - 10.1093/hmg/ddn370
M3 - Article
C2 - 19000992
AN - SCOPUS:58749115233
VL - 18
SP - 428
EP - 439
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 3
ER -