AMPK: A Target for Drugs and Natural Products With Effects on Both Diabetes and Cancer
Open accessAbstract
The AMP-activated protein kinase (AMPK) is a highly conserved sensor of cellular energy that appears to have arisen at an early stage during eukaryotic evolution. In 2001 it was shown to be activated by metformin, currently the major drug for treatment for type 2 diabetes. Although the known metabolic effects of AMPK activation are consistent with the idea that it mediates some of the therapeutic benefits of metformin, as discussed below it now appears unlikely that AMPK is the sole target of the drug. AMPK is also activated by several natural plant products derived from traditional medicines, and the mechanisms by which they activate AMPK are discussed. One of these is salicylate, probably the oldest medicinal agent known to humankind. The salicylate prodrug salsalate has been shown to improve metabolic parameters in subjects with insulin resistance and prediabetes, and whether this might be mediated in part by AMPK is discussed. 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.
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An increase in AMP decreases adenylate cyclase activation and thereby lowers glucagon release.
“Furthermore, an increase in AMP also decreases adenylate cyclase activation and thereby lowers glucagon release (129).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [129]
Inhibition of mitochondrial complex 1 decreases the ATP/AMP ratio, activating AMPK.
“This inhibition would in turn decrease the ATP/AMP ratio activating AMPK (127–129).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [129]
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References 80 · Cited by 458
Research works printed but not linked: 1
- [32]Bailey CJ Campbell IW Chan JCN Davidson JA Howlett HCS Ritz P, Eds. Metformin: The Gold Standard. Chichester, U.K., John Wiley & Sons, 2007
- Authors
- Hardie, D. G.
- Affiliations
- University of Dundee (GB)
- Corresponding author
- Hardie, D. Grahame
- ORCID
- Hardie, D. Grahame
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2013-06-14
- Volume
- 62
- Issue
- 7
- Pages
- 2164-2172
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC3712072
- OpenAlex
- W2125344123
- Cited by
- 458
- References
- 80
- Citations by year
- 2026: 21 · 2025: 25 · 2024: 19 · 2023: 26 · 2022: 27 · 2021: 33 · 2020: 48 · 2019: 30 · 2018: 48 · 2017: 48 · 2016: 39 · 2015: 45 · 2014: 44 · 2013: 5
- FWCI
- 4.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion, cc-by-nc-nd)
- Funders
- Wellcome Trust (097726)
- Cancer Research UK (15101)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- AMPK, metformin, type 2 diabetes, cancer prevention, natural products, traditional medicine, salicylates, salsalate, aspirin, insulin resistance, prediabetes, energy sensing, therapeutic target
- MeSH terms
- Adenylate Kinase, Diabetes Mellitus, Type 2, Energy Metabolism, Humans, Hypoglycemic Agents, Metformin, Neoplasms
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