Role of AMPK in nutrient sensing and cancer


  • Prof Grahame Hardie

    University of Dundee

Project summary

I have shown that the protein AMPK senses the energy state of living cells, much like the system in a mobile phone that monitors battery charge, and adjusts cellular metabolism accordingly. For example, it senses energy shortage in muscles during exercise and is responsible for many of the short- and long-term adaptations that occur after exercise, many of which have health benefits. Several chronic human conditions, such as obesity or type 2 diabetes, can be regarded as disorders of energy balance and AMPK is also crucial here, which is why some existing diabetes drugs work partly by switching it on. I have been investigating  how AMPK senses availability of carbohydrate independently of cellular energy, whether it senses other cellular metabolites that bind in the so-called ’ADaM’ site on the protein, if it senses availability of glycogen, the main intracellular reserve of carbohydrate, and why some genes encode AMPK subunits amplified in human cancers. 

The findings will yield insights relevant to major human diseases and could suggest that AMPK inhibitors would enhance the effect of drugs currently used for chemotherapy in cancer, reducing unwanted side effects.