D G Hardie


Affiliation: University of Dundee
Country: UK


  1. Hawley S, Ford R, Smith B, Gowans G, Mancini S, Pitt R, et al. The Na+/Glucose Cotransporter Inhibitor Canagliflozin Activates AMPK by Inhibiting Mitochondrial Function and Increasing Cellular AMP Levels. Diabetes. 2016;65:2784-94 pubmed publisher
    ..Because phosphorylation of ACC by AMPK is known to lower liver lipid content, these data suggest a potential additional benefit of canagliflozin therapy compared with other SGLT2 inhibitors. ..
  2. Hardie D. Organismal carbohydrate and lipid homeostasis. Cold Spring Harb Perspect Biol. 2012;4: pubmed publisher
    ..Overnutrition can dysregulate these pathways and have damaging consequences, causing insulin resistance and type 2 diabetes. ..
  3. Hardie D. Metformin-acting through cyclic AMP as well as AMP?. Cell Metab. 2013;17:313-4 pubmed publisher
    ..Several targets to account for its therapeutic effects have been proposed, but a recent paper suggests a novel mechanism in which it antagonizes the cyclic AMP-dependent effects of glucagon on hepatic glucose production. ..
  4. Fyffe F, Hawley S, Gray A, Hardie D. Cell-Free Assays to Measure Effects of Regulatory Ligands on AMPK. Methods Mol Biol. 2018;1732:69-86 pubmed publisher
    ..AMPK is also activated by ligands that bind in the ADaM site, which is located between the α and β subunits. In this chapter we describe cell-free assays that can be used to study these varied activation mechanisms. ..
  5. Hardie D. The LKB1-AMPK pathway-friend or foe in cancer?. Cancer Cell. 2013;23:131-2 pubmed publisher
    ..In this issue of Cancer Cell, Shackelford and colleagues show, paradoxically, that biguanides are more effective in the treatment of mouse tumors that lack a functional LKB1-AMPK pathway. ..
  6. Ross F, Jensen T, Hardie D. Differential regulation by AMP and ADP of AMPK complexes containing different γ subunit isoforms. Biochem J. 2016;473:189-99 pubmed publisher
    ..Thus, AMPK complexes containing different γ subunit isoforms respond differently to changes in AMP, ADP or ATP. These differences may tune the responses of the isoforms to fit their differing physiological roles. ..
  7. Hardie D. Molecular Pathways: Is AMPK a Friend or a Foe in Cancer?. Clin Cancer Res. 2015;21:3836-40 pubmed publisher
    ..Paradoxically, however, a complete loss of AMPK function, which appears to be rare in human cancers, may be deleterious to survival of tumor cells. AMPK can therefore be either a friend or a foe in cancer, depending on the context. ..
  8. Hardie D. AMPK: positive and negative regulation, and its role in whole-body energy homeostasis. Curr Opin Cell Biol. 2015;33:1-7 pubmed publisher
    ..Finally, AMPK is negatively regulated by phosphorylation of the 'ST loop' within the catalytic subunit. ..
  9. request reprint
    Hardie D. Biochemistry. Balancing cellular energy. Science. 2007;315:1671-2 pubmed

More Information


  1. Hardie D. Sensing of energy and nutrients by AMP-activated protein kinase. Am J Clin Nutr. 2011;93:891S-6 pubmed publisher
    ..Most of these agents activate AMPK because they inhibit mitochondrial function. ..
  2. Hawley S, Fyffe F, Russell F, Gowans G, Grahame Hardie D. Intact Cell Assays to Monitor AMPK and Determine the Contribution of the AMP-Binding or ADaM Sites to Activation. Methods Mol Biol. 2018;1732:239-253 pubmed publisher
  3. Dandapani M, Hardie D. AMPK: opposing the metabolic changes in both tumour cells and inflammatory cells?. Biochem Soc Trans. 2013;41:687-93 pubmed publisher
    ..Evidence supporting this view is discussed, including our findings that AMPK is activated by the classic anti-inflammatory drug salicylate. ..
  4. Hardie D. AMP-activated protein kinase: maintaining energy homeostasis at the cellular and whole-body levels. Annu Rev Nutr. 2014;34:31-55 pubmed publisher
    ..AMPK is activated by two widely used clinical drugs, metformin and aspirin, and also by many natural products of plants that are either derived from traditional medicines or are promoted as "nutraceuticals." ..
  5. Hardie D. AMPK: a target for drugs and natural products with effects on both diabetes and cancer. Diabetes. 2013;62:2164-72 pubmed publisher
    ..Interestingly, there is evidence that both metformin and aspirin provide some protection against development of cancer in humans, and whether AMPK might be involved in these effects is also discussed. ..
  6. Hardie D. AMPK--sensing energy while talking to other signaling pathways. Cell Metab. 2014;20:939-52 pubmed publisher
    ..It is also becoming clear that there is a substantial amount of crosstalk between the AMPK pathway and other signaling pathways that promote cell growth and proliferation, and this will be discussed. ..
  7. Fogarty S, Ross F, Vara Ciruelos D, Gray A, Gowans G, Hardie D. AMPK Causes Cell Cycle Arrest in LKB1-Deficient Cells via Activation of CAMKK2. Mol Cancer Res. 2016;14:683-95 pubmed publisher
    ..Mol Cancer Res; 14(8); 683-95. ©2016 AACR. ..
  8. Hardie D. An Oncogenic Role for the Ubiquitin Ligase UBE2O by Targeting AMPK-?2 for Degradation. Cancer Cell. 2017;31:163-165 pubmed publisher
    ..In this issue of Cancer Cell, Vila et al. report that UBE2O, a ubiquitin ligase overexpressed in some human cancers, specifically triggers the ubiquitination and degradation of AMPK-?2. ..
  9. Hardie D. Energy sensing by the AMP-activated protein kinase and its effects on muscle metabolism. Proc Nutr Soc. 2011;70:92-9 pubmed publisher
    ..We are working on the hypothesis that this ensures that glycogen synthesis is rapidly activated when glycogen becomes depleted after exercise, but is switched off again as soon as glycogen stores are replenished. ..
  10. Hardie D. AMPK: a key regulator of energy balance in the single cell and the whole organism. Int J Obes (Lond). 2008;32 Suppl 4:S7-12 pubmed publisher
    ..Novel drugs activating AMPK may also have potential for the treatment of obesity. ..
  11. Ross F, Hawley S, Auciello F, Gowans G, Atrih A, Lamont D, et al. Mechanisms of Paradoxical Activation of AMPK by the Kinase Inhibitors SU6656 and Sorafenib. Cell Chem Biol. 2017;24:813-824.e4 pubmed publisher
    ..By contrast, sorafenib, a kinase inhibitor in clinical use, activates AMPK indirectly by inhibiting mitochondrial metabolism and increasing cellular AMP:ADP and/or ADP:ATP ratios. ..
  12. Hardie D, Schaffer B, Brunet A. AMPK: An Energy-Sensing Pathway with Multiple Inputs and Outputs. Trends Cell Biol. 2016;26:190-201 pubmed publisher
    ..We particularly focus on methods for identifying the AMPK target recognition motif and how it can be used to predict new substrates. ..
  13. Hardie D. Keeping the home fires burning: AMP-activated protein kinase. J R Soc Interface. 2018;15: pubmed publisher
    ..Indeed, some existing drugs such as metformin and aspirin, which were derived from traditional herbal remedies, appear to work, in part, by activating AMPK. ..
  14. Hadad S, Baker L, Quinlan P, Robertson K, Bray S, Thomson G, et al. Histological evaluation of AMPK signalling in primary breast cancer. BMC Cancer. 2009;9:307 pubmed publisher
    ..Reduced signalling via the AMPK pathway, and the inverse relationship with histological grade and axillary node metastasis, suggests that AMPK re-activation could have therapeutic potential in breast cancer. ..
  15. request reprint
    Hawley S, Davison M, Woods A, Davies S, Beri R, Carling D, et al. Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated protein kinase. J Biol Chem. 1996;271:27879-87 pubmed
    ..A., Selbert, M. A., Goldstein, E. G., Edelman, A. M., Carling, D., and Hardie, D. G. (1995) J. Biol. Chem. 270, 27186-27191). ..
  16. Vara Ciruelos D, Dandapani M, Gray A, Egbani E, Evans A, Hardie D. Genotoxic Damage Activates the AMPK-α1 Isoform in the Nucleus via Ca2+/CaMKK2 Signaling to Enhance Tumor Cell Survival. Mol Cancer Res. 2018;16:345-357 pubmed publisher
    ..Furthermore, α1-selective inhibitors might enhance the anticancer effects of genotoxic-based therapies. Mol Cancer Res; 16(2); 345-57. ©2017 AACR. ..
  17. Salt I, Hardie D. AMP-Activated Protein Kinase: An Ubiquitous Signaling Pathway With Key Roles in the Cardiovascular System. Circ Res. 2017;120:1825-1841 pubmed publisher
  18. Rena G, Hardie D, Pearson E. The mechanisms of action of metformin. Diabetologia. 2017;60:1577-1585 pubmed publisher
    ..More work is required to truly understand how this drug works in its target population: individuals with type 2 diabetes. ..
  19. Lin S, Hardie D. AMPK: Sensing Glucose as well as Cellular Energy Status. Cell Metab. 2018;27:299-313 pubmed publisher
    ..Glucose sensing at the lysosome, in which AMPK and other components of the activation complex act antagonistically with another key nutrient sensor, mTORC1, may have been one of the ancestral roles of AMPK. ..
  20. Hardie D, Alessi D. LKB1 and AMPK and the cancer-metabolism link - ten years after. BMC Biol. 2013;11:36 pubmed publisher
    ..This finding represented the first clear link between AMPK and cancer. Here we briefly discuss how this discovery came about, and describe some of the insights, especially into the role of AMPK in cancer, that have followed from it. ..
  21. Hardie D, Ross F, Hawley S. AMP-activated protein kinase: a target for drugs both ancient and modern. Chem Biol. 2012;19:1222-36 pubmed publisher
    ..We review the mechanisms of AMPK activation by these and other drugs, and by natural products derived from traditional herbal medicines. ..
  22. Hardie D, Ross F, Hawley S. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol. 2012;13:251-62 pubmed publisher
    ..Finally, recent studies reveal that AMPK conserves ATP levels through the regulation of processes other than metabolism, such as the cell cycle and neuronal membrane excitability. ..
  23. Hardie D. AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. Genes Dev. 2011;25:1895-908 pubmed publisher
    ..Both tumor cells and viruses establish mechanisms to down-regulate AMPK, allowing them to escape its restraining influences on growth. ..
  24. Hardie D, Carling D, Gamblin S. AMP-activated protein kinase: also regulated by ADP?. Trends Biochem Sci. 2011;36:470-7 pubmed publisher
    ..We also discuss the role of the carbohydrate-binding module on the ? subunit and the mechanisms by which it is activated by drugs and xenobiotics such as metformin and resveratrol. ..
  25. request reprint
    Hardie D. The AMP-activated protein kinase pathway--new players upstream and downstream. J Cell Sci. 2004;117:5479-87 pubmed
  26. request reprint
    Hardie D. PLANT PROTEIN SERINE/THREONINE KINASES: Classification and Functions. Annu Rev Plant Physiol Plant Mol Biol. 1999;50:97-131 pubmed
  27. request reprint
    Hardie D, Scott J, Pan D, Hudson E. Management of cellular energy by the AMP-activated protein kinase system. FEBS Lett. 2003;546:113-20 pubmed
    ..A survey of the range of downstream targets for this important signalling pathway is presented. ..
  28. request reprint
    Hardie D, Carling D. The AMP-activated protein kinase--fuel gauge of the mammalian cell?. Eur J Biochem. 1997;246:259-73 pubmed
    ..AMPK/SNF1 homologues are found in higher plants, and this protein-kinase cascade appears to be an ancient system which evolved to protect cells against the effects of nutritional or environmental stress. ..