IRS1 and Insulin resistance: As suggested by several studies, proinflammatory cytokines and endoplasmic stress contribute to insulin resistance by activating serine kinases c-Jun N-terminal kinase (JNK) and I kappa B kinase (IKK-b), which are responsible for increasing the phosphorylation of IRS1 at serine sites (serine 302 pS302 and serine 307 pS307).