Cited by 479Metabolism, Diabetes, and CancerDiabetes Treatment and ManagementNatural Antidiabetic Agents Studies

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Molecular mechanism of action of metformin: old or new insights?

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Rena, Graham, Pearson, Ewan R., Sakamoto, Kei·2013·Diabetologia

DOI 10.1007/s00125-013-2991-0PMC PMC3737434

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Abstract

Metformin is the first-line drug treatment for type 2 diabetes. Globally, over 100 million patients are prescribed this drug annually. Metformin was discovered before the era of target-based drug discovery and its molecular mechanism of action remains an area of vigorous diabetes research. An improvement in our understanding of metformin's molecular targets is likely to enable target-based identification of second-generation drugs with similar properties, a development that has been impossible up to now. The notion that 5' AMP-activated protein kinase (AMPK) mediates the anti-hyperglycaemic action of metformin has recently been challenged by genetic loss-of-function studies, thrusting the AMPK-independent effects of the drug into the spotlight for the first time in more than a decade. Key AMPK-independent effects of the drug include the mitochondrial actions that have been known for many years and which are still thought to be the primary site of action of metformin. Coupled with recent evidence of AMPK-independent effects on the counter-regulatory hormone glucagon, new paradigms of AMPK-independent drug action are beginning to take shape. In this review we summarise the recent research developments on the molecular action of metformin.

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Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)
(1998) · The Lancet · doi:10.1016/s0140-6736(98)07037-8 · Cited by 8,247
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
AMPK: a nutrient and energy sensor that maintains energy homeostasis
Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3311 · Cited by 4,602
Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group.
(1998) · PubMed · Cited by 4,290
Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)
Inzucchi, S. E., Bergenstal, R. M., Buse, J. B., Diamant, M., Ferrannini, E., Nauck, M., Peters, A. L., Tsapas, A., Wender, R., & Matthews, D. R. (2012) · Diabetologia · doi:10.1007/s00125-012-2534-0 · Cited by 3,919
Anorexigenic and Orexigenic Hormone Modulation of Mammalian Target of Rapamycin Complex 1 Activity and the Regulation of Hypothalamic Agouti-Related Protein mRNA Expression
Watterson, K. R., Bestow, D., Gallagher, J. R., Hamilton, D. L., Ashford, F. B., Meakin, P. J., & Ashford, M. L. J. (2012) · Neurosignals · doi:10.1159/000334144 · Cited by 3,395
AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism
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
The selectivity of protein kinase inhibitors: a further update
Bain, J., Plater, L., Elliott, M., Shpiro, N., Hastie, C. J., McLauchlan, H., Klevernic, I. V., Arthur, J. S. C., Alessi, D. R., & Cohen, P. (2007) · Biochemical Journal · doi:10.1042/bj20070797 · Cited by 2,522
Metformin and reduced risk of cancer in diabetic patients
Evans, J. M. M., Donnelly, L. A., Emslie-Smith, A. M., Alessi, D. R., & Morris, A. D. (2005) · BMJ · doi:10.1136/bmj.38415.708634.f7 · Cited by 2,388
Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain
OWEN, M. R., DORAN, E., & HALESTRAP, A. P. (2000) · Biochemical Journal · doi:10.1042/bj3480607 · Cited by 2,157

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Show all 98 references

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Ray RK, Kauffman GB (1999) Metal and non-metal biguanide complexes. New Age International Publishers, New Delhi
Kazda CM, Garhyan P, Kelly RP et al (2012) 12-week treatment with glucagon receptor antagonist LY2409021 significantly lowers HbA1c and is well tolerated in patients with type 2 diabetes mellitus. Diabetologia 55(Suppl 1):S51, Abstr. 112

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Authors: Rena, G., Pearson, E. R., & Sakamoto, K.
Affiliations: University of Dundee (GB)
École Polytechnique Fédérale de Lausanne (CH)
Corresponding author: Rena, Graham
Sakamoto, Kei
ORCID: Rena, Graham
Pearson, Ewan R.
Sakamoto, Kei
Venue: Diabetologia
Publisher: Springer Science and Business Media LLC
Published: 2013-07-09
Volume: 56
Issue: 9
Pages: 1898-1906
ISSN: 0012-186X (ISSN-L)
1432-0428
DOI: 10.1007/s00125-013-2991-0
PMC: PMC3737434
OpenAlex: W2025130292
Cited by: 479
References: 98
Citations by year: 2026: 9 · 2025: 22 · 2024: 20 · 2023: 33 · 2022: 22 · 2021: 52 · 2020: 33 · 2019: 38 · 2018: 58 · 2017: 51 · 2016: 37 · 2015: 52 · 2014: 43 · 2013: 8
FWCI: 4.39
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
creativecommons.org/licenses/by-nc/2.0 (unspecified)
Locations: Diabetologia (publishedVersion, cc-by-nc)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
reroDoc Digital Library (submittedVersion)
Discovery Research Portal (University of Dundee) (submittedVersion)
Funders: Medical Research Council (MR/K012924/1)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
Keywords: metformin, molecular mechanisms of action, type 2 diabetes, AMPK, glucagon, therapeutic target
MeSH terms: Diabetes Mellitus, Type 2, Energy Metabolism, Gluconeogenesis, Humans, Metformin, Models, Biological, AMP-Activated Protein Kinases

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