title: Connexins protect mouse pancreatic β cells against apoptosis.
abstract: Type 1 diabetes develops when most insulin-producing β cells of the pancreas are killed by an autoimmune attack. The in vivo conditions modulating the sensitivity and resistance of β cells to this attack remain largely obscure. Here, we show that connexin 36 (Cx36), a trans-membrane protein that forms gap junctions between β cells in the pancreatic islets, protects mouse β cells against both cytotoxic drugs and cytokines that prevail in the islet environment at the onset of type 1 diabetes. We documented that this protection was at least partially dependent on intercellular communication, which Cx36 and other types of connexin channels establish within pancreatic islets. We further found that proinflammatory cytokines decreased expression of Cx36 and that experimental reduction or augmentation of Cx36 levels increased or decreased β cell apoptosis, respectively. Thus, we conclude that Cx36 is central to β cell protection from toxic insults.
authors: Department of Cell Physiology and Metabolism, University of Geneva, Medical School, Geneva, Switzerland.
authors: Philippe
authors: P
authors: Klee
authors: Florent
authors: F
authors: Allagnat
authors: Helena
authors: H
authors: Pontes
authors: Manon
authors: M
authors: Cederroth
authors: Anne
authors: A
authors: Charollais
authors: Dorothée
authors: D
authors: Caille
authors: Aurore
authors: A
authors: Britan
authors: Jacques-Antoine
authors: JA
authors: Haefliger
authors: Paolo
authors: P
authors: Meda
mesh_terms: D000496:Alloxan / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002450:Cell Communication; D060833:Cellular Microenvironment; D017630:Connexins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D017629:Gap Junctions / Q000502:physiology; D018628:Gene Dosage; D007328:Insulin / Q000235:genetics; D007371:Interferon-gamma / Q000633:toxicity; D053583:Interleukin-1beta / Q000633:toxicity; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000096:biosynthesis; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013311:Streptozocin / Q000494:pharmacology / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity; D000097004:Gap Junction delta-2 Protein
chemical_list: D000496:Alloxan; D017630:Connexins; D007328:Insulin; D007371:Interferon-gamma; D053583:Interleukin-1beta; D009569:Nitric Oxide; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D013311:Streptozocin; D014409:Tumor Necrosis Factor-alpha; D000097004:Gap Junction delta-2 Protein