Abstract
Interleukin-1β (IL-1) is cytotoxic to beta-cells. II-1 induces a “race” between protective, (e.g., oxidative stress proteins, manganese superoxide dismutase (MnSOD) and deleterious (free oxygen and nitric oxide radicals) events in all cell types. By means of non-radioactive in situ hybridization, Northern and dot blot analysis and functional studies, IL-1 (150 pg/ml) induction of heme oxygenase (HO) 1 and 2, MnSOD and nitric oxide synthases (NOS) was studied in isolated rat islets in vitro during 0-48 h of exposure to IL-1. HO1, HO2 and MnSOD mRNAs were maximally induced after 1, 6 and 24 h, respectively and the inducible form of NOS (NO2-release) after 6-12 h and the constitutive, calcium-dependent NOS after 24-48 h. Beta-cell function (insulin release) deteriorated after 6 h, maximally at 24 h. This suggests that in beta-cells the deleterious events prevail. Thus, beta-cell destruction in the initial phases of IDDM pathogenesis may be a stepwise, well-defined series of molecular events.
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Cuartero, B., Hougaard, D., Pociot, F. et al. BETA-CELL DESTRUCTION IN INSULIN-DEPENDENT DIABETES MELLITUS (IDDM)- A STEPWISE SERIES OF EVENTS. Pediatr Res 33 (Suppl 5), S74 (1993). https://doi.org/10.1203/00006450-199305001-00425
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DOI: https://doi.org/10.1203/00006450-199305001-00425