Proapoptotic BH3-only protein bid is essential for death receptor-induced apoptosis of pancreatic β-cells

Abstract

OBJECTIVE-Apoptosis of pancreatic β-cells is critical in both diabetes development and failure of islet transplantation. The role in these processes of pro-and antiapoptotic Bcl-2 family proteins, which regulate apoptosis by controlling mitochondrial integrity, remains poorly understood. We investigated the role of the BH3-only protein Bid and the multi-BH domain proapoptotic Bax and Bak, as well as prosurvival Bcl-2, in β-cell apoptosis. RESEARCH DESIGN AND METHODS-We isolated islets from mice lacking Bid, Bax, or Bak and those overexpressing Bcl-2 and exposed them to Fas ligand, tumor necrosis factor (TNF)-α, and proinflammatory cytokines or cytotoxic stimuli that activate the mitochondria..