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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652
Resveratrol improves health and survival of mice on a high-calorie diet
Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., Prabhu, V. V., Allard, J. S., Lopez-Lluch, G., Lewis, K., et al. (2006) · Nature · doi:10.1038/nature05354 · Cited by 4,290
Yamauchi, T., Kamon, J., Minokoshi, Y., Ito, Y., Waki, H., Uchida, S., Yamashita, S., Noda, M., Kita, S., Ueki, K., et al. (2002) · Nature Medicine · doi:10.1038/nm788 · Cited by 4,238
TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914
AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849
AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity
Cantó, C., Gerhart-Hines, Z., Feige, J. N., Lagouge, M., Noriega, L., Milne, J. C., Elliott, P. J., Puigserver, P., & Auwerx, J. (2009) · Nature · doi:10.1038/nature07813 · Cited by 3,300
Kahn, B. B., Alquier, T., Carling, D., & Hardie, D. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2004.12.003 · Cited by 2,799
Self-citationAMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α
Jäger, S., Handschin, C., St.-Pierre, J., & Spiegelman, B. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705070104 · Cited by 2,491
AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy
Hardie, D. G. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2249 · Cited by 2,261
Self-citationMitochondrial dysfunction and type 2 diabetes
Lowell, B. B., & Shulman, G. I. (2005) · Science · doi:10.1126/science.1104343 · Cited by 2,070
Flagged first, then by citations
Cited by
Sorted by citations
Speakman, J. R., & Mitchell, S. E. (2011) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2011.07.001 · Cited by 797
Luen Tang, B. (2016) · Molecules and Cells · doi:10.14348/molcells.2016.2318 · Cited by 740
Placental Origins of Chronic Disease
Burton, G. J., Fowden, A. L., & Thornburg, K. L. (2016) · Physiological Reviews · doi:10.1152/physrev.00029.2015 · Cited by 717
S-adenosylmethionine in Liver Health, Injury, and Cancer
Lu, S. C.-L., & Mato, J. M. (2012) · Physiological Reviews · doi:10.1152/physrev.00047.2011 · Cited by 565
Rabinovitch, R. C., Samborska, B., Faubert, B., Ma, E. H., Gravel, S.-P., Andrzejewski, S., Raissi, T. C., Pause, A., St.-Pierre, J., & Jones, R. G. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.09.026 · Cited by 543
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
