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.1 AICAR is a selective activator of AMPK in both hepatocytes and adipocytes.2 At 0.5 mM it inhibits the synthesis of fatty acids and sterols and inactivates HMG-CoA reductase in rat hepatocytes.2 AICAR (0.5 mM) inhibits insulin-stimulated glucose uptake to 62% of controls and reduces GLUT4 translocation 2.5-fold in 3T3-L1 adipocytes.3 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.4
1
Hardie, D.G., and Carling, D. The AMP-activated protein kinase. Fuel gauge of the mammalian cell?Eur J Biochem246259-273(1997).
2
Corton, J.M., Gillespie, J.G., Hawley, S.A., et al. 5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells?Eur J Biochem229558-565(1995).
3
Salt, I.P., Connell, J.M.C., and Gould, G.W. 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) inhibits insulin-stimulated glucose transport in 3T3-L1 adipocytes. Diabetes491649-1656(2000).
4
Ayasolla, K.R., Giri, S., Singh, A.K., et al. 5-aminoimidazole-4-carboxamide-I-beta-4-ribofuranoside (AICAR) attenuates the expression of LPS- and Aβ peptide-induced inflammatory mediators in astroglia. J Neuroinflammation21-21(2005).
Corton, J.M., Gillespie, J.G., Hawley, S.A., et al. 5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells?Eur J Biochem229558-565(1995).
Hardie, D.G., and Carling, D. The AMP-activated protein kinase. Fuel gauge of the mammalian cell?Eur J Biochem246259-273(1997).
Ayasolla, K.R., Giri, S., Singh, A.K., et al. 5-aminoimidazole-4-carboxamide-I-beta-4-ribofuranoside (AICAR) attenuates the expression of LPS- and Aβ peptide-induced inflammatory mediators in astroglia. J Neuroinflammation21-21(2005).
Salt, I.P., Connell, J.M.C., and Gould, G.W. 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) inhibits insulin-stimulated glucose transport in 3T3-L1 adipocytes. Diabetes491649-1656(2000).