Evidence demonstrates that exogenous nitric oxide (NO) and the NO produced by inducible nitric oxide synthase (iNOS) can induce insulin resistance in muscle. Here, we investigated whether this insulin resistance could be mediated by S-nitrosation of proteins involved in early steps of the insulin signal transduction pathway. Exogenous NO donated by S-nitrosoglutathione (GSNO) induced in vitro and in vivo S-nitrosation of the insulin receptor β subunit (IRβ) and protein kinase B/Akt (Akt) and reduced their kinase activity in muscle. Insulin receptor substrate (IRS)-1 was also rapidly S-nitrosated, and its expression was reduced after chronic GSNO treatment. In two distinct models of insulin resistance associated with enhanced iNOS expression—diet-induced obesity and the ob/ob diabetic mice—we observed enhanced S-nitrosation of IRβ/IRS-1 and Akt in muscle. Reversal of S-nitrosation of these proteins by reducing iNOS expression yielded an improvement in insulin action in both animal models. Thus, S-nitrosation of proteins involved in insulin signal transduction is a novel molecular mechanism of iNOS-induced insulin resistance.

The synthesis of anisotropic metallic nanoparticles (NPs) has been a field of intense and challenging research in the past decade. In this communication, we report on the reproducible and highly controllable synthesis of monodisperse branched gold nanoparticles in a droplet-based microfluidics platform. The process has been automated by adapting two different bulk synthetic strategies to microdroplets, acting as microreactors, for NP synthesis: a surfactant-free synthesis and a surfactant-assisted synthesis. Microdroplets were generated in two different microfluidic devices designed to accommodate the requirements of both bulk syntheses. The epitaxial growth of AuNSTs inside the microdroplets allowed for a fine control of reagent mixing and local concentrations during particle formation. This is the first time branched gold NPs have been synthesised in a microfluidics platform. The monodispersity of the product was comparable to the synthesis in bulk, proving the potential of this technology for the continuous synthesis of high quality anisotropic NPs with improved reproducibility.