The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Leptin modulates β cell expression of IL-1 receptor antagonist and release of IL-1β in human islets
Open accessAbstract
High concentrations of glucose induce β cell production of IL-1β, leading to impaired β cell function and apoptosis in human pancreatic islets. IL-1 receptor antagonist (IL-1Ra) is a naturally occurring antagonist of IL-1β and protects cultured human islets from glucotoxicity. Therefore, the balance of IL-1β and IL-1Ra may play a crucial role in the pathogenesis of diabetes. In the present study, we observed expression of IL-1Ra in human pancreatic β cells of nondiabetic individuals, which was decreased in tissue sections of type 2 diabetic patients.In vitro, chronic exposure of human islets to leptin, a hormone secreted by adipocytes, decreased β cell production of IL-1Ra and induced IL-1β release from the islet preparation, leading to impaired β cell function, caspase-3 activation, and apoptosis. Exogenous addition of IL-1Ra protected cultured human islets from the deleterious effects of leptin. Antagonizing IL-1Ra by introduction of small interfering RNA to IL-1Ra into human islets led to caspase-3 activation, DNA fragmentation, and impaired β cell function. Moreover, siIL-1Ra enhanced glucose-induced β cell apoptosis. These findings demonstrate expression of IL-1Ra in the human β cell, providing localized protection against leptin- and glucose-induced islet IL-1β.
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Cites
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Self-citationDivergent Roles of SHP-2 in ERK Activation by Leptin Receptors
Bjørbæk, C., Buchholz, R. M., Davis, S. M., Bates, S. H., Pierroz, D. D., Gu, H., Neel, B. G., Myers, M. G., & Flier, J. S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007439200 · Cited by 364
Leptin Receptors Expressed on Pancreatic β-Cells
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Cited by
Type 2 diabetes as an inflammatory disease
Donath, M. Y., & Shoelson, S. E. (2011) · Nature Reviews Immunology · doi:10.1038/nri2925 · Cited by 3,737
Self-citationInflammation in obesity, diabetes, and related disorders
Rohm, T. V., Meier, D. T., Olefsky, J. M., & Donath, M. Y. (2022) · Immunity · doi:10.1016/j.immuni.2021.12.013 · Cited by 2,066
Self-citationInterleukin-1-receptor antagonist in type 2 diabetes mellitus
Larsen, C. M., Faulenbach, M., Vaag, A., Vølund, A., Ehses, J. A., Seifert, B., Mandrup-Poulsen, T., & Donath, M. Y. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa065213 · Cited by 1,798
Self-citationThe vagus nerve and the inflammatory reflex – linking immunity and metabolism
Pavlov, V. A., & Tracey, K. J. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.189 · Cited by 1,040
Metabolic Syndrome and Insulin Resistance: Underlying Causes and Modification by Exercise Training
Roberts, C. K., Hevener, A. L., & Barnard, R. J. (2013) · Comprehensive Physiology · doi:10.1002/cphy.c110062 · Cited by 831
Metadata
- Authors
- Maedler, K., Sergeev, P., Ehses, J. A., Mathe, Z., Bosco, D., Berney, T., Dayer, J.-M., Reinecke, M., Halban, P. A., & Donath, M. Y.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2004-05-12
- Volume
- 101
- Issue
- 21
- Pages
- 8138-8143
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2006313514
- Cited by
- 249
- References
- 9
- FWCI
- 9.69
- Type
- journal article
- Language
- en
- Open access
- green
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- Maedler, K., Sergeev, P., Ehses, J. A., Mathe, Z., Bosco, D., Berney, T., Dayer, J.-M., Reinecke, M., Halban, P. A., & Donath, M. Y. (2004). Leptin modulates β cell expression of IL-1 receptor antagonist and release of IL-1β in human islets. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0305683101
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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