FIGURE 3.

The inhibitory of melatonin on endoplasmic reticulum (ER) stress. When ER stress occurs, GRP78 is separated from PERK, ATF6, and IRE1α, which activates three signal pathways and leads to increased levels of downstream molecules, including p‐elf2α, p‐ATF4, CHOP, p‐IRE1α, p‐JNK, and cleaved caspase 12, which eventually leads to cell apoptosis. Melatonin activates Sirt1, which is inhibited by hyperglycemia in cardiomyocytes, and inhibits the PERK‐p‐elf2α‐ATF4‐CHOP signaling pathway, thus reducing ER stress and reducing cardiomyocyte apoptosis in diabetic patients. ATF‐6, activated transcription factor 6; IRE1α, inositol‐requiring protein‐1α; PERK, protein kinase RNA‐like endoplasmic reticulum kinase