This pro-inflammatory microenvironment interferes with insulin signaling through multiple molecular mechanisms, including increased serine phosphorylation and decreased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), thereby inhibiting normal activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, ultimately leading to the development of insulin resistance (28, 29). The gene discussed is INS; the disease is Insulin resistance.