Transgenic overexpression of human Bcl-2 in islet β cells inhibits apoptosis but does not prevent autoimmune destruction

Abstract

Insulin-dependent diabetes mellitus results when > 90% of the insulin-producing β cells in the pancreatic islets are killed as a result of autoimmune attack by T cells. During the progression to diabetes, islet β cells die as a result of different insults from the immune system. Agents such as perforin and granzymes, CD95 ligand and tumor necrosis factor-α, or cytokines and free-radicals have all been shown to cause β cell apoptosis. The anti-apoptotic protein, Bcl-2, might protect against some of these stimuli. We have therefore generated transgenic mice expressing human Bcl-2 in their islet β cells. Although Bcl-2 was able to prevent apoptosis induced by cytotoxic agents against β cells in vitro, Bcl-2 alone could not prevent or ameliorate cytotoxic or autoimmune β cell damage in vivo.