Modulation of ER Stress in Human Type 1 Diabetic Islets Through Combined Use of Stress Inducer and Inhibitor Treatments

Given the predominance of alpha cells and marked differences in ER stress-related gene expression in Type 1 Diabetes (T1D) islets, we explored the modulation of ER stress pathways using targeted treatments. Overall design: T1D islets from three separate donors, pre-stained with DTZ, were selectively treated with thapsigargin (TG) and/or taurodeoxycolic acid (TUDCA) for a total of 12 samples. A total of 100 islets for each experimental condition were meticulously selected, excluding any cluster-like structures indicative of acinar cells, and subjected to RNA sequencing. The treatment regimen included inducing ER stress using TG (250 nM) and mitigating it in T1D islets with TUDCA (100 ng/ml), TG, or their combination. These treatments were administered for 24 hours prior to RNA-seq analysis to evaluate the changes in ER stress response.