The key pathogenetic mechanism for GH-induced glucose intolerance is insulin resistance (IR)7,8 and it is mediated by GH-induced increased lipolysis, inhibition of the post-receptor insulin signalling by blockade of insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3-kinase (PI3K) signalling, induction of suppressor of cytokine signalling pathway, and decreased expression of adiponectin and visfatin4,9–19. The gene discussed is IRS1; the disease is Insulin resistance.