IRS2 and Glucose intolerance: In animal models, maternal high-fat diet (HFD) induces hypermethylation of the insulin receptor substrate 2 (Irs2) gene and hypomethylation of hypomethylated mitogen-activated protein kinase 4 (Map2k4) gene in the offspring liver, which is associated with reduced insulin receptor substrate expression and increased glucose intolerance [25].