For instance, downregulated NAD-dependent protein deacetylase sirtuin 1 (SIRT1) promoted stress signaling pathways such as IRE1-JNK in T1DM (75), and PERK-CHOP and IRE1-caspase 12 signaling in T2DM (76), resulting in ER-mediated apoptosis and cardiac dysfunction. Here, MAPK8 is linked to type 2 diabetes mellitus.