A complete destruction of pancreatic β-cells, caused by an autoimmune reaction, underlies the development of type 1 diabetes. In type 2 diabetes, a partial reduction in β-cell mass is also observed and may contribute to the impaired capacity of the endocrine pancreas to secrete enough insulin to compensate for the development of insulin resistance in peripheral tissues. Because both forms of diabetes are associated with apoptosis-dependent loss of β-cell mass, identifying novel proteins involved in the control of apoptosis may lead to novel approaches to preserve β-cell mass and the insulin secretion capacity of the endocrine pancreas.
Dhaval Patel et al. show that siRNA-mediated Clic4 silencing in βTC-tet cells or its genetic inactivation in islets β-cells reduces the sensitivity of these cells to cytokines- or palmitic acid-induced apoptosis. Clic4 knockdown reduces the degradation rate of Bcl-2 and Bad and increases the total level of phosphorylated Bad, possibly as a result of Clic4 interaction with the proteasome.