The mechanism by which PRAK knockout induced insulin resistance is likely to be related to the down-regulation of irisin and the suppression of IRS-1, AMPK α, and ERK1/2 phosphorylation since the myocardium of PRAK knockout mice showed reductions in irisin and IRS-1, AMPKα, and ERK phosphorylations. Here, MAPK3 is linked to Insulin resistance.