IRS1 and Insulin resistance: In his seminal article, Hotamisligil has extensively discussed the role of JNK, particularly the JNK1 isoform, as a central mediator in the pathophysiology of insulin resistance mainly by IRS-1 serine phosphorylation and subsequent inhibition of insulin actions, through activation of inflammatory signaling cascades (Wellen and Hotamisligil, 2005; Hotamisligil and Erbay, 2008).