Nicotinic acetylcholine receptor signaling regulates inositol-requiring enzyme 1α activation to protect β-cells against terminal unfolded protein response under irremediable endoplasmic reticulum stress.

Our findings suggest that nAChR signaling regulates IRE1α activation to protect β-cells from the T-UPR and apoptosis under ER stress partly through α7 nAChR. Targeting nAChR signaling to inhibit the T-UPR cascade may therefore hold therapeutic promise by thwarting β-cell death in diabetes.