ERN1 and Insulin resistance: Indeed, a growing body of evidence suggests that UPR and insulin resistance are interconnected through at least 2 mechanisms: 1) IRE1α pathway induces c-Jun N-terminal kinase (JNK) phosphorylation which inhibits IRS; 2) PERK and IRE1α pathway activate transcription factors such as nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) which migrate to the nucleus and induce the transcription of cytokines known to contribute to the development of insulin resistance [23], [25], [26].