Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Maedler, K; Sergeev, P; Ehses, JA; Mathe, Z; Bosco, D; Berney, T; Dayer, JM; Reinecke, M; Halban, PA; Donath, MY.
Leptin modulates beta cell expression of IL-1 receptor antagonist and release of IL-1beta in human islets.
Proc Natl Acad Sci U S A. 2004; 101(21):8138-8143
Doi: 10.1073/pnas.0305683101
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- Co-Autor*innen der Med Uni Graz
- Mathe Zoltan
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- Abstract:
- High concentrations of glucose induce beta cell production of IL-1beta, leading to impaired beta cell function and apoptosis in human pancreatic islets. IL-1 receptor antagonist (IL-1Ra) is a naturally occurring antagonist of IL-1beta and protects cultured human islets from glucotoxicity. Therefore, the balance of IL-1beta 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 beta 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 beta cell production of IL-1Ra and induced IL-1beta release from the islet preparation, leading to impaired beta 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 beta cell function. Moreover, siIL-1Ra enhanced glucose-induced beta cell apoptosis. These findings demonstrate expression of IL-1Ra in the human beta cell, providing localized protection against leptin- and glucose-induced islet IL-1beta.
- Find related publications in this database (using NLM MeSH Indexing)
- Apoptosis - drug effects
- Caspase 3 -
- Caspases - metabolism
- Cell Survival - drug effects
- Diabetes Mellitus, Type 2 - genetics
- Diabetes Mellitus, Type 2 - metabolism
- Diabetes Mellitus, Type 2 - pathology
- Down-Regulation - drug effects
- Gene Expression Regulation - drug effects
- Humans -
- Interleukin 1 Receptor Antagonist Protein -
- Interleukin-1 - antagonists & inhibitors
- Interleukin-1 - metabolism
- Islets of Langerhans - drug effects
- Islets of Langerhans - enzymology
- Islets of Langerhans - metabolism
- Islets of Langerhans - pathology
- Leptin - antagonists & inhibitors
- Leptin - pharmacology
- Sialoglycoproteins - antagonists & inhibitors
- Sialoglycoproteins - genetics
- Sialoglycoproteins - metabolism
- Sialoglycoproteins - pharmacology
- Signal Transduction - drug effects