Moderate ER stress, facilitated by IL-1β, initiates protective mechanisms in pancreatic β-cells ameliorating dysfunction and diminishing death induced by inflammatory cytokines.

SÉTULA C.; ORELLANO M.; ARGAÑARÁS, M.; SCELZAFIGUEREDO, A.; SPINEDI, E.; ANDREONE L.; PERONE MJ.

Boston

Congreso; Annual Meeting The Endocrine Society; 2024

Type 1 and type 2 diabetes share common features, encompassing islet inflammation,β-cell dysfunction and the eventual reduction in both the number and mass of β-cells.The organism´s resilience against higher doses of a harmful substance can be bolsteredthrough the induction of mild stress responses, achieved by exposing it to lowconcentrations of the said agent. Our objective was to evaluate whether physiologicalconcentrations of IL-1β prompt adaptive mechanisms that protect β-cells from thedistinctive inflammatory milieu associated with diabetes.We employed INS-1E insulinoma and isolated mouse islets and measured NO by Griess,cell viability (MTT) and death (Hoechst/PI, microscopic fluorescence and Annexin VPE/7-AAD, flow cytometry), mRNA by RT-qPCR, NF-kB (immunofluorescence), insulin(ELISA) and proteins by Western blot (WB). GSIS (glucose-stimulated insulin secretion)index was calculated as the ratio of insulin released during 1h under stimuli of20mM/2mM glucose. Results are presented as mean ± SD, n ³3 independentexperiments. Comparison between groups was carried out using paired or unpairedStudent ́s t-test or ANOVA followed by Bonferroni ́s multiple comparison test, asappropriate.Mild endoplasmic reticulum (ER) stress was induced in β-cells through a 72h incubationwith 10 pg/ml IL-1β (IL-1blow). Cytokine-induced damage was triggered by 100 pg/ml IL1b + 5 ng/ml IFNg for 16h (CYT). IL-1blow protects INS-1E from the decrease inmitochondrial reduction potential triggered by CYT, diminishes cell death (p