Figure 4.

The ER stress network and members activated in rodent and human β-cells exposed to LC-FFA. (A) Within the ER lumen, misfolded and unfolded proteins accumulate, sequestering and binding to BIP, which triggers the activation of PERK, IRE1, and ATF6. ER stress sensors are then activated, initiating the UPR pathway which, downstream results in the upregulation of genes that alleviate ER stress. (B) With prolonged ER stress, ER stress sensor activation initiates predominantly the PERK- and IRE1-dependent ER stress pathways to induce an apoptotic response. Activating transcription factor 4 (ATF4); Ccl-2 homologous antagonist/killer (BAK); Bcl-2-associated X protein (BAX); BH3 interacting-domain death agonist (BID); Immunoglobulin heavy-chain binding protein (BIP); Cytochrome c (C); CCAAT-enhancer-binding protein homologous protein (CHOP); eukaryotic translation initiation factor 2α (eIF2α); inositol 1,4,5-triphosphate (IP3R); inositol requiring ER-to-nucleus signal kinase 1 (IRE1); c-Jun N-terminal kinase (JNK1); Nuclear factor ĸB (NFĸB); PKR-like ER kinase (PERK); IRE1 dependent decay (RIDD); SH₃ homology-associated BTK binding protein (Sab); sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA); site-1 protease (S1P); TNF receptor-associated factor 2 (TRAF2); X-box binding 1 (XBP1). Information of potential mechanisms extracted with reference to (76–79).