Serine phosphorylation of IRSs inhibits insulin signal transduction and contributes to peripheral insulin resistance [201], which is partly mediated by pro-inflammatory cytokines; prolonged resistance is exacerbated by aging and obesity, resulting in glucose intolerance, hyperlipidemia, hypertension, polycystic ovarian syndrome, and type 2 diabetes mellitus [202]. The gene discussed is INS; the disease is type 2 diabetes mellitus.