Cited by 374Metabolism, Diabetes, and CancerSirtuins and Resveratrol in MedicineBiochemical and Molecular Research

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Sensing of energy and nutrients by AMP-activated protein kinase

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Hardie, D Grahame·2011·The American Journal of Clinical Nutrition

DOI 10.3945/ajcn.110.001925

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Abstract

AMP-activated protein kinase (AMPK) is a cellular energy sensor that exists in almost all eukaryotes. Genetic studies in lower eukaryotes suggest that the ancestral role of AMPK was in response to starvation for a carbon source and that AMPK is involved in life-span extension in response to caloric restriction. In mammals, AMPK is activated by an increasing cellular AMP:ATP ratio (which signifies a decrease in energy) caused by metabolic stresses that interfere with ATP production (eg, hypoxia) or that accelerate ATP consumption (eg, muscle contraction). Because glucose deprivation can increase the AMP:ATP ratio, AMPK can also act as a glucose sensor. AMPK activation occurs by a dual mechanism that involves allosteric activation and phosphorylation by upstream kinases. Once activated, AMPK switches on catabolic pathways that generate ATP (eg, the uptake and oxidation of glucose and fatty acids and mitochondrial biogenesis) while switching off ATP-consuming, anabolic pathways (eg, the synthesis of lipids, glucose, glycogen, and proteins). In addition to the acute effects via direct phosphorylation of metabolic enzymes, AMPK has longer-term effects by regulating transcription. These features make AMPK an ideal drug target in the treatment of metabolic disorders such as insulin resistance and type 2 diabetes. The antidiabetic drug metformin (which is derived from an herbal remedy) works in part by activating AMPK, whereas many xenobiotics or "nutraceuticals," including resveratrol, quercetin, and berberine, are also AMPK activators. Most of these agents activate AMPK because they inhibit mitochondrial function.

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Authors: Hardie, D. G.
Affiliations: University of Dundee (GB)
Corresponding author: Hardie, D Grahame
ORCID: Hardie, D Grahame
Venue: The American Journal of Clinical Nutrition
Publisher: Elsevier BV
Published: 2011-04
Volume: 93
Issue: 4
Pages: 891S-896S
ISSN: 0002-9165 (ISSN-L)
DOI: 10.3945/ajcn.110.001925
OpenAlex: W2123729941
Cited by: 372
References: 67
Citations by year: 2026: 12 · 2025: 18 · 2024: 14 · 2023: 15 · 2022: 15 · 2021: 20 · 2020: 26 · 2019: 23 · 2018: 21 · 2017: 17 · 2016: 27 · 2015: 16 · 2014: 38 · 2013: 40 · 2012: 41
FWCI: 4.30
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 4343 d)
Locations: American Journal of Clinical Nutrition (publishedVersion)
PubMed (publishedVersion)
Discovery Research Portal (University of Dundee) (publishedVersion)
Funders: Wellcome Trust
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
Keywords: AMPK, nutrient sensing, AMP/ATP ratio, glucose detection, starvation response, caloric restriction, lifespan extension, allosteric activation, mitochondrial biogenesis, metabolic regulation, transcriptional regulation, insulin resistance, type 2 diabetes, metformin, nutraceuticals, resveratrol, quercetin, berberine
MeSH terms: Adenosine Monophosphate, Adenosine Triphosphate, Animals, Energy Metabolism, Gene Expression Regulation, Glucose, Metabolic Diseases, Metformin, Mitochondria, Phosphorylation, Plant Extracts, Signal Transduction, AMP-Activated Protein Kinases

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Sensing of energy and nutrients by AMP-activated protein kinase

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