IRS1 and Insulin resistance: In fact, TNF-α promotes the reduction of insulin receptor substrate 1 (IRS-1) mRNA and GLUT4mRNA, leading to insulin resistance and hyperglycemia [12] Moreover, Massaro and coworkers showed that peroxisome proliferator activated receptor (PPAR) alpha/gamma agonists attenuated insulin resistance in human adipocytes, reducing pro-inflammatory mediators including IL-6, CXC-L10 and monocyte chemoattractant protein (MCP-1), supporting the pathogenic role of inflammation in DM development [13].