IRS2 and diabetes mellitus: An animal-based study found that maternal high fat diet leads to hypermethylation of insulin receptor substrate-2 gene (IRS-2) and hypomethylation of mitogen-activated protein kinase kinase-4 gene (MAP2K4) in mice offspring; thus, decreasing and increasing the gene expression, respectively, and elevating pup's risk of developing diabetes in the future (86).