IDE deficiency enhances the unfolded protein response (UPR) in mouse and human beta cells under proteotoxic stress, but not at baseline, indicating a role for IDE in modulating cellular stress adaptation.

When the enzyme that breaks down insulin and a related protein is missing, these proteins build up inside insulin-producing cells. This overload stresses the cell's protein-making factory, forcing it to turn on a emergency alarm system that tries to fix the mess. Normally, the cell would slow down protein production to recover, but without this enzyme, the alarm stays on too long and the cell keeps making too much protein anyway. This causes the cell to swell with misfolded proteins, break its storage containers, and eventually fail to release insulin properly, even though it makes more of it.