The activation of c-Jun N-terminal kinase (JNK) and IKK, both serine kinases, disrupts insulin signaling and promotes insulin resistance through the phosphorylation of insulin receptor substrates, IRS-1 and IRS-2, in serine residues, causing their inactivation, in opposition to phosphorylation in tyrosine residues associated with insulin-dependent IRS-1 activation in healthy subjects [36]. The gene discussed is IRS1; the disease is Insulin resistance.