Pancreatic ␤-cells are sensitive to a number of proapoptotic stimuli. Thus, apoptosis is an important part of the physiological neonatal remodeling of the endocrine pancreas, and a number of pathological stimuli involved in type 1 and type 2 diabetes have been shown to elicit ␤-cell apoptosis. Factors of relevance to type 1 diabetes include proinflammatory cytokines, nitric oxide, and reactive oxygen species as well as Fas ligand. Recent findings that free fatty acids, glucose, sulfonylurea,

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... amylin cause ␤-cell apoptosis in vitro suggest that programmed cell death may also be involved in the pathogenesis of type 2 diabetes. Furthermore, there is evidence favoring a convergence in signaling pathways toward common effectors of ␤-cell apoptosis elicited by stimuli implicated in the pathogenesis of type 1 and type 2 diabetes. Therefore, recent studies involving the stimuli and signaling pathways of ␤-cell apoptosis-in particular, mitogen-and stressactivated protein kinases-will be reviewed. It is concluded that immunological, inflammatory, and metabolic signals cause ␤-cell apoptosis, and the possibility that these signals converge toward a common ␤-cell death signaling pathway should be investigated further. Diabetes 50 (Suppl. 1):S58-S63, 2001