[Insulin resistance and nitric oxide: molecular mechanisms and pathophysiological associations]

Subclinical inflammation that primarily arises in adipose tissue as a result of its excessive infiltration by immunocompetent cells represents one of the typical etiopathogenetic mechanisms underlying the development of insulin resistance and type 2 diabetes. Immunocompetent cells together with adipocytes are a major source of proinflammatory cytokines triggering proinflammatory cascades that in turn interfere with postreceptor insulin signalling cascade. Recent studies have suggested that inducible nitric oxide synthase plays a key role in this process. Obesity is associated with increased inducible nitric oxide synthase mRNA expression, with subsequent overproduction of nitric oxide and reactive nitrogen species leading to S-nitrosylation of proteins involved in insulin signalling cascade. These post-translational modifications decrease their activity and eventually lead to insulin resistance. Number of experimental studies demonstrated that inhibition of inducible nitric oxide synthase attenuates insulin resistance. The aim of this review is to summarize the current knowledge about the physiology and patophysiology of nitric oxide and inducible nitric oxide synthase with respect to its relationship to insulin resistance and to discuss the possibility of improvement of insulin resistance and type 2 diabetes mellitus by modulating inducible nitric oxide synthase activity.