MAPK8 and Insulin resistance: Specifically, Tanti et al. found that phosphorylation of IRS1 by JNK inhibits its interaction with insulin receptor (IR), causes defective IRS1 tyrosine phosphorylation, and importantly, abrogates IRS downstream PI3K-AKT signaling, thus promoting FOXO1-mediated gluconeogenesis, and finally causing insulin resistance (Figure 5A) [85,86,87].