IRS2 and type 2 diabetes mellitus: Cullin7, one of the genes down regulated on silencing Ankrd2, is an E3 ubiquitin ligase that targets IRS-1 for degradation by the proteasome [41] and an increase in the IGF-IR was found to up-regulate Pax6 and glucagon which in turn activated the IRS-2/MAPK pathway that could lead to dysregulation associated with type 2 diabetes [42].