The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.
Sensing of energy and nutrients by AMP-activated protein kinase
Open accessAbstract
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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In the citing paper
“These same pathways are shared with a number of the nutrient sensing mechanisms [3,4].”
From New strategies in sport nutrition to increase exercise performance (2016) · cites this paper as [4]
In the citing paper
“This kinase is activated in response to the increase of the AMP/ATP ratio, for example, after deprivation of glucose, whereas its activity is reduced when cells are full of energy and the AMP/ATP ratio decreases”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Hardie, 2011
In the citing paper
“AMPK is one of the major sensitive energy sensors in cells and organisms.”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Hardie, 2011
In the citing paper
“Opposite regulators are AMP-activated kinase (AMPK) and sirtuins that are activated when energy uptake is limited (Hardie, 2011).”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Hardie, 2011
In the citing paper
“This kinase is activated in response to the increase of the AMP/ATP ratio, for example, after deprivation of glucose, whereas its activity is reduced when cells are full of energy and the AMP/ATP ratio decreases (Hardie, 2011).”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Hardie, 2011
In the citing paper
“Classically, it acts to promote glucose uptake and mitochondrial biogenesis, while reducing energy demands by inhibiting mTORC1 (239).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [239]
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Cites
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Metadata
- 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)
- 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
- 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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