title: Cx36 makes channels coupling human pancreatic beta-cells, and correlates with insulin expression.
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.
authors.affiliation: Surgical Research Unit, Department of Surgery, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Véronique
authors.initials: V
authors.lastname: Serre-Beinier
authors.forename: Domenico
authors.initials: D
authors.lastname: Bosco
authors.forename: Laurence
authors.initials: L
authors.lastname: Zulianello
authors.forename: Anne
authors.initials: A
authors.lastname: Charollais
authors.forename: Dorothée
authors.initials: D
authors.lastname: Caille
authors.forename: Eric
authors.initials: E
authors.lastname: Charpantier
authors.forename: Benoit R
authors.initials: BR
authors.lastname: Gauthier
authors.forename: Giuseppe R
authors.initials: GR
authors.lastname: Diaferia
authors.forename: Ben N
authors.initials: BN
authors.lastname: Giepmans
authors.forename: Roberto
authors.initials: R
authors.lastname: Lupi
authors.forename: Piero
authors.initials: P
authors.lastname: Marchetti
authors.forename: Shaoping
authors.initials: S
authors.lastname: Deng
authors.forename: Léo
authors.initials: L
authors.lastname: Buhler
authors.forename: Thierry
authors.initials: T
authors.lastname: Berney
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cirulli
authors.forename: Paolo
authors.initials: P
authors.lastname: Meda
mesh_terms: D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D017629:Gap Junctions / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D000097004:Gap Junction delta-2 Protein
chemical_list: D017630:Connexins; D007328:Insulin; D020033:Protein Isoforms; D000097004:Gap Junction delta-2 Protein