Citation | Grahame Hardie identified the AMP-activated protein kinase (AMPK), its regulation by 5'AMP and phosphorylation and several physiological roles. He introduced the concept that AMPK is a sensor of cellular energy charge and showed that it stimulates glucose uptake into muscle during exercise. This led him to propose that the AMPK cascade was a target for anti-diabetic drugs, a prediction later vindicated by the discovery that metformin activates the AMPK. Recently, Hardie identified the AMP-binding domains and their mutation in human disease and discovered that the tumour suppressor LKB1 is the "upstream" activator of AMPK. His work has opened up the AMPK system, which has become a major field of research with 400 papers per year being published and international conferences being held regularly on this topic. |