Cx36 makes channels coupling human pancreatic beta-cells, and correlates with insulin expression.
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.
Serre-Beinier
Véronique
V
Surgical Research Unit, Department of Surgery, Geneva University Hospitals, Geneva, Switzerland.
Bosco
Domenico
D
Zulianello
Laurence
L
Charollais
Anne
A
Caille
Dorothée
D
Charpantier
Eric
E
Gauthier
Benoit R
BR
Diaferia
Giuseppe R
GR
Giepmans
Ben N
BN
Lupi
Roberto
R
Marchetti
Piero
P
Deng
Shaoping
S
Buhler
Léo
L
Berney
Thierry
T
Cirulli
Vincenzo
V
Meda
Paolo
P
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
D017630:Connexins; D007328:Insulin; D020033:Protein Isoforms; D000097004:Gap Junction delta-2 Protein