AMP-Activated Protein Kinase: Maintaining Energy Homeostasis at the Cellular and Whole-Body Levels

D Grahame Hardie (Lead / Corresponding author)

    Research output: Contribution to journalReview articlepeer-review

    193 Citations (Scopus)


    The adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway arose early during evolution of eukaryotic cells, when it appears to have been involved in the response to glucose starvation and perhaps also in monitoring the output of the newly acquired mitochondria. Due to the advent of hormonal regulation of glucose homeostasis, glucose starvation is a less frequent event for mammalian cells than for single-celled eukaryotes. Nevertheless, the AMPK system has been preserved in mammals where, by monitoring cellular AMP:adenosine triphosphate (ATP) and adenosine diphosphate (ADP):ATP ratios and balancing the rates of catabolism and ATP consumption, it maintains energy homeostasis at a cell-autonomous level. In addition, hormones involved in maintaining energy balance at the whole-body level interact with AMPK in the hypothalamus. 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."

    Original languageEnglish
    Pages (from-to)31-55
    Number of pages25
    JournalAnnual Review of Nutrition
    Early online date15 May 2014
    Publication statusPublished - Jul 2014


    • AMP-Activated Protein Kinases
    • Animals
    • Energy Intake
    • Energy Metabolism
    • Homeostasis
    • Humans
    • Models, Biological
    • Signal Transduction
    • Journal Article
    • Research Support, Non-U.S. Gov't
    • Review


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