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Title

Connexins protect mouse pancreatic β cells against apoptosis

Authors
Allagnat, Florent
Pontes, Helena
Cederroth, Manon
Caille, Dorothée
Haefliger, Jacques-Antoine
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Published in Journal of Clinical Investigation. 2011, vol. 121, no. 12, p. 4870-9
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.
Keywords Alloxan/pharmacology/toxicityAnimalsApoptosis/drug effectsCell CommunicationCellular MicroenvironmentConnexins/antagonists & inhibitors/deficiency/genetics/physiologyDiabetes Mellitus, Experimental/chemically induced/metabolism/pathology/prevention & controlGap Junctions/physiologyGene DosageInsulin/geneticsInterferon-gamma/toxicityInterleukin-1beta/toxicityIslets of Langerhans/drug effects/metabolism/pathologyMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicNitric Oxide/biosynthesisPromoter Regions, GeneticRNA InterferenceRNA, Small Interfering/pharmacologyRatsRecombinant Fusion Proteins/physiologyStreptozocin/pharmacology/toxicityTumor Necrosis Factor-alpha/toxicity
Identifiers
PMID: 22056383
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Article (Published version) (4.4 MB) - public document Free access
Structures
Research group Couplage cellulaire et connexines (136)
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(ISO format)
KLEE, Philippe et al. Connexins protect mouse pancreatic β cells against apoptosis. In: Journal of Clinical Investigation, 2011, vol. 121, n° 12, p. 4870-9. https://archive-ouverte.unige.ch/unige:25464

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Deposited on : 2013-01-14

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