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J Clin Invest. 2011 Dec;121(12):4870-9. doi: 10.1172/JCI40509. Epub 2011 Nov 7.

Connexins protect mouse pancreatic β cells against apoptosis.

Author information

1
Department of Cell Physiology and Metabolism, University of Geneva, Medical School, Geneva, Switzerland.

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.

PMID:
22056383
PMCID:
PMC3225984
DOI:
10.1172/JCI40509
[Indexed for MEDLINE]
Free PMC Article

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