AMP-activated protein kinase (AMPK) functions as a metabolic sensor that regulates lipid and glucose metabolism to maintain cellular energy homeostasis and to protect against metabolic stress.AICAR is a selective activator of AMPK in both hepatocytes and adipocytes. At 0.5 mM it inhibits the synthesis of fatty acids and sterols and inactivates HMG-CoA reductase in rat hepatocytes. AICAR (0.5 mM) inhibits insulin-stimulated glucose uptake to 62% of controls and reduces GLUT4 translocation 2.5-fold in 3T3-L1 adipocytes. It also blocks the expression of pro-inflammatory cytokines (TNF-α/IL-1β and IL-6), iNOS, COX-2, and MnSOD genes in glial cells and macrophages by inhibiting NFκB and C/EBP pathways.