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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.

SUBMITTER: Klee P 

PROVIDER: S-EPMC3225984 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Connexins protect mouse pancreatic β cells against apoptosis.

Klee Philippe P   Allagnat Florent F   Pontes Helena H   Cederroth Manon M   Charollais Anne A   Caille Dorothée D   Britan Aurore A   Haefliger Jacques-Antoine JA   Meda Paolo P  

The Journal of clinical investigation 20111107 12


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 d  ...[more]

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