Hormesis mediated by IL-1b protects pancreatic -cells from dysfunction and death induced by inflammatory cytokines

SETULA, C; ORELLANO, MS; ARGANARAS, MILAGROS; ANDREONE, L; PERONE, MJ

Congreso; Reunion Anual de Sociedades de Biociencias (SAIC, SAB, AAFE, AACYTAL); 2023

Both type 1 and type 2 diabetes share islet inflammation. Hormesis is a phenomenon by which a harmful substance administered to an organism in small doses provides resistance to subsequent contacts with higher doses. We aimed to assess if physiological concentrations of IL-1 induce hormesis leading to adaptive mechanisms, safeguarding -cells against the characteristic inflammatory environment of diabetes.We employed INS-1E insulinoma and pancreatic islets and measured NO by Griess, viability (MTT), death (Hoechst/PI, microscopic fluorescence; Annexin V-PE/7-AAD, flow cytometry), mRNA by RT-qPCR, NF-B (immunofluorescence) and insulin (ELISA). GSIS (glucose-stimulated insulin secretion) index was calculated as the ratio of insulin released during 1h under stimuli of 20mM/2mM glucose. Hormesis was induced by incubation with 10 pg/ml IL-1 for 72h (IL-1low). Cytokine-induced damage was triggered by 100 pg/ml IL-1 + 5 ng/ml IFN for 16h (CYT).Hormesis induced by IL-1low protects INS-1E from the decrease in mitochondrial reduction potential triggered by CYT, diminishes cell death (p