IRS1 and atherosclerosis: Given the elevated oxidative stress levels and abnormal lipid metabolism reported previously in PON2-deficient mice [25, 38], Bourquard et al. hypothesized that atherosclerosis may be accompanied by impaired hepatic insulin signaling and showed that PON2 deficiency is associated with inhibitory insulin-mediated phosphorylation of hepatic insulin receptor substrate-1 (IRS-1) [39].