INS and Alzheimer disease: Hyperglycaemia can cause an increase in nitrogen species, which in turn, leads to the pathological nitrogenation of IDE to form S-nitrosylated IDE, decreasing the enzymatic activity.12 Evidence from murine models and humans show significantly higher levels of S-nitrosylated IDE in patients with AD compared with controls.12 Nitrosative stress, a widely recognised feature of AD which follows a similar pathogenesis to oxidative stress (mitochondrial generation of nitrogen-containing-free radicals) has been shown to have no effect on the ability of IDE to bind insulin.