Fig. 8: IL-1β^low helps preserve GSIS and modulates the transcriptomic profile.

A INS-1E cells and B isolated mouse islets (5 IEQ/well) were preconditioned with IL-1β^low and then challenged or not with CYT (IL-1β 100 pg/ml + IFN-γ 5 ng/ml) or iCYT (IL-1β 100 pg/ml + IFN-γ 5 ng/ml + TNF-α 8 ng/ml), respectively. After 16 h, a glucose-stimulated insulin secretion (GSIS) assay was performed. Insulin levels in conditioned media were measured by ELISA. The insulin secretion index (20 mM/2 mM glucose) is expressed as mean ± SD, n = 6. (*) p < 0.05, (**) p < 0.01. C–E INS-1E cells were treated as in (A), and bulk RNA-seq was performed, n = 3. C Principal component analysis (PCA) of transcriptomic profiles shows distinct clustering by condition. Each point represents an individual sample, with the variance explained indicated on each axis. D Heatmap of log2CPM-normalized data (Z-score transformed), filtered to include differentially expressed genes (DEGs) identified from all pairwise comparisons. Colors indicate higher (red) and lower (blue) expression relative to the mean for a curated subset of these genes. Genes and samples were hierarchically clustered based on expression similarity. E Gene set enrichment analysis (GSEA) of IL-1β^low-preconditioned INS-1E cells exposed to CYT, compared to CYT-challenged cells without preconditioning, using Hallmark gene sets: pancreatic β-cells, G2M checkpoint, inflammatory response, TNF-α signaling via NF-κB, unfolded protein response, and apoptosis. Normalized enrichment scores (NES) and p-values are shown for each pathway.