Tumor Necrosis Factor-Alpha: Role in Development of Insulin Resistance and Pathogenesis of Type 2 Diabetes Mellitus.

Pathogenesis of type 2 diabetes mellitus (T2DM) and development of insulin resistance are characterized by multi-stimuli factors notably glucolipotoxicity, generation of reactive oxygen species (ROS), epigenetic factors, activation of various transcriptional mediated pathways along with the augmented levels of various pro-inflammatory cytokines. Among the various pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) is one the most important pro-inflammatory mediator that is critically involved in the development of insulin resistance and pathogenesis of T2DM. TNF-α is mainly produced in adipocytes and/or peripheral tissues, and induces tissue-specific inflammation through the involvement of generation of ROS and activation of various transcriptional mediated pathways. The raised level of TNF-α induces insulin resistance in adipocytes and peripheral tissues by impairing the insulin signaling through serine phosphorylation that leads to the development of T2DM. Anti-TNF-α treatment strategies have been developed to reduce the incidence of insulin resistance and development of T2DM. In this article, we have briefly described how TNF-α plays crucial role to induce insulin resistance and pathogenesis of T2DM. To block the inflammatory responses by blocking TNF-α and TNF-α signaling may be an effective strategy for the treatment of insulin resistance and T2DM. J. Cell. Biochem. 119: 105-110, 2018.