Connexins protect mouse pancreatic beta cells against apoptosis.

摘要

Type 1 diabetes develops when most insulin-producing beta cells of the pancreas are killed by an autoimmune attack. The in vivo conditions modulating the sensitivity and resistance of beta cells to this attack remain largely obscure. Here, we show that connexin 36 (Cx36), a trans-membrane protein that forms gap junctions between beta cells in the pancreatic islets, protects mouse beta 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 beta cell apoptosis, respectively. Thus, we conclude that Cx36 is central to beta cell protection from toxic insults.