Hyperglycemia and free fatty acids disturb the proteostasis, which leads to the accumulation of unfolded/misfolded proteins in the ER lumen, under ER stress, activating transcription factor 4 (ATF4), inositol requiring enzyme 1alpha (IRE1α) and protein kinase R-like endoplasmic reticulum kinase (PERK) are activated, which leads to the activation of downstream pro-apoptotic genes (caspase-4 or caspase-12), resulting in apoptosis [28]. This evidence concerns the gene ATF4 and Hyperglycemia.