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

SETULA, CAROLINA; ORELLANO, MIRANDA SOL; ARGAÑARAS, MILAGROS; ANDREONE LUZ; PERONE, MARCELO JAVIER

Mar del Plata

Congreso; LXVIII Reunión Anual de la SAIC; 2023

Both type 1 and type 2 diabetes share pancreatic 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 used INS-1E rat cells and mouse 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