beta-cell apoptosis: stimuli and signaling.
Pancreatic beta-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 beta-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, and amylin cause beta-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 beta-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 beta-cell apoptosis-in particular, mitogen- and stress-activated protein kinases-will be reviewed. It is concluded that immunological, inflammatory, and metabolic signals cause beta-cell apoptosis, and the possibility that these signals converge toward a common beta-cell death signaling pathway should be investigated further.
Steno Diabetes Center, Gentofte, Denmark. tmpo@novo.dk
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Mandrup-Poulsen
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D009569:Nitric Oxide / Q000502:physiology; D015398:Signal Transduction
D016207:Cytokines; D009569:Nitric Oxide; D020928:Mitogen-Activated Protein Kinases