Cx36 makes channels coupling human pancreatic β-cells, and correlates with insulin expression
| Autor: | Benoit R. Gauthier, Laurence Zulianello, Eric Charpantier, Thierry Berney, Paolo Meda, Dorothée Caille, Piero Marchetti, Ben N G Giepmans, Anne Charollais, Vincenzo Cirulli, Véronique Serre-Beinier, Giuseppe R. Diaferia, Shaoping Deng, Domenico Bosco, Leo Buhler, Roberto Lupi |
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| Přispěvatelé: | Swiss National Science Foundation, Juvenile Diabetes Research Foundation, European Commission, Larry L. Hillblom Foundation, National Institutes of Health (US), Center for Liver, Digestive and Metabolic Diseases (CLDM) |
| Rok vydání: | 2009 |
| Předmět: |
Connexin
Diabetes Mellitus Type 2/genetics/metabolism Gene Expression Connexins Gap Junctions/genetics/metabolism Cell membrane 0302 clinical medicine Insulin-Secreting Cells SECRETING CELLS Gene expression Insulin Protein Isoforms Lipid raft Genetics (clinical) Cells Cultured GENE-EXPRESSION Pancreas/metabolism 0303 health sciences MOUSE-BRAIN Protein Isoforms/genetics/metabolism ISLET TRANSPLANTATION Gap Junctions Articles General Medicine 3. Good health Cell biology medicine.anatomical_structure B-CELLS Islets of Langerhans/metabolism ZONULA OCCLUDENS-1 Pancreas CONNEXIN36 Gene isoform medicine.medical_specialty 030209 endocrinology & metabolism Connexins/genetics/metabolism Biology Islets of Langerhans 03 medical and health sciences Insulin-Secreting Cells/metabolism Internal medicine INVIVO MODULATION Genetics medicine ION CHANNELS Humans ddc:612 Molecular Biology Cell Membrane/genetics/metabolism 030304 developmental biology Messenger RNA Insulin/genetics/metabolism Pancreatic islets Cell Membrane GAP-JUNCTION CHANNELS Endocrinology Diabetes Mellitus Type 2 sense organs |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Human molecular genetics, Vol. 18, No 3 (2009) pp. 428-39 Human Molecular Genetics Human Molecular Genetics; Vol 18 Human Molecular Genetics, 18(3), 428-439. Oxford University Press |
| ISSN: | 1460-2083 0964-6906 |
| Popis: | 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. The Swiss National Science Foundation (310000-122430 to P.Me), the Juvenile Diabetes Research Foundation (1-2005-1084 to V.C., 1-2007-158 to P.Me), the National Institute of Health (DK55183 to V.C.), the European Union (FP6-Integrated Project EuroDia LSHM-CT-2006-518153 to P.Ma; FP-7 BETAIMAGE 222980 to P.Me), Novo Nordisk (to P.Me) and The Larry L. Hillblom Foundation (to V.C.). Image analysis was performed at The National Center for Microscopy and Imaging Research (NIH grant RR4050 to M. Ellisman). Fresh human islets were provided by the Cell Isolation and Transplantation Center |
| Databáze: | OpenAIRE |
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