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beta-cell apoptosis: stimuli and signaling
1Steno Diabetes Center, Gentofte, Denmark. tmpo@novo.dk
Abstract:
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.
Insights
Apoptosis, or programmed cell death, is crucial in pancreatic remodeling and diabetes pathogenesis. Immune, inflammatory, and metabolic signals converge, triggering beta-cell death, warranting further investigation into common signaling pathways.
Area of Science:
- Endocrinology
- Cell Biology
- Immunology
Background:
- Pancreatic beta-cells undergo apoptosis during physiological neonatal remodeling.
- Pathological stimuli in type 1 and type 2 diabetes induce beta-cell apoptosis.
- Proinflammatory cytokines, nitric oxide, reactive oxygen species, and Fas ligand are implicated in type 1 diabetes.
- Free fatty acids, glucose, sulfonylurea, and amylin induce beta-cell apoptosis in vitro, suggesting a role in type 2 diabetes.
Purpose of the Study:
- To review stimuli and signaling pathways of beta-cell apoptosis.
- To investigate the convergence of signaling pathways toward common effectors of beta-cell apoptosis.
- To highlight the role of mitogen- and stress-activated protein kinases in beta-cell apoptosis.
Main Methods:
- Review of recent studies on beta-cell apoptosis stimuli.
- Analysis of signaling pathways involved in beta-cell death.
- Examination of evidence for convergence in apoptosis signaling.
Main Results:
- Immunological, inflammatory, and metabolic signals are identified as causes of beta-cell apoptosis.
- Evidence suggests convergence of signaling pathways toward common effectors of beta-cell apoptosis.
- Mitogen- and stress-activated protein kinases are key players in beta-cell apoptosis signaling.
Conclusions:
- Beta-cell apoptosis is influenced by diverse signals relevant to diabetes.
- Further investigation is needed to confirm the convergence of these signals onto a common beta-cell death pathway.
- Understanding these pathways is critical for developing therapeutic strategies for diabetes.