2012/04/20 by Simon A. Hawley, Morgan D. Fullerton, Fiona A. Ross +11 · 4 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Metabolism, Diabetes, and Cancer #Autophagy in Disease and Therapy #Pancreatic function and diabetes
paper · doi:10.1126/science.1215327
openalex publication_date 2012/04/20 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/02
Salicylate, a plant product, has been in medicinal use since ancient times. More recently, it has been replaced by synthetic derivatives such as aspirin and salsalate, both of which are rapidly broken down to salicylate in vivo. At concentrations reached in plasma after administration of salsalate or of aspirin at high doses, salicylate activates adenosine monophosphate-activated protein kinase (AMPK), a central regulator of cell growth and metabolism. Salicylate binds at the same site as the synthetic activator A-769662 to cause allosteric activation and inhibition of dephosphorylation of the activating phosphorylation site, threonine-172. In AMPK knockout mice, effects of salicylate to increase fat utilization and to lower plasma fatty acids in vivo were lost. Our results suggest that AMPK activation could explain some beneficial effects of salsalate and aspirin in humans.