The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism.

By S. Hawley, Anne E. Gadalla, G. S. Olsen, D. Hardie. Diabetes, 2002

713 citations recorded by the source corpus.

Subfields: Endocrinology, Diabetes and Metabolism, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/3274c8048f51e7f6128297e4651e29eb1dc4c188

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Endocrinology, Diabetes and Metabolism

1. D. Hardie
2. G. Steinberg
3. S. Hawley
4. Bruce E. Kemp
5. B. K. Pedersen
6. R. Shaw
7. T. Borody
8. A. Khoruts

In Molecular Biology

1. D. Hardie
2. G. Steinberg
3. S. Hawley
4. David Carling
5. Bruce E. Kemp
6. Fiona A. Ross
7. R. Shaw
8. M. Towler

In Surgery

1. D. Hardie
2. G. Steinberg
3. David Carling
4. Bruce E. Kemp
5. S. Hawley
6. Fiona A. Ross
7. M. Towler
8. K. Green

Citations in the corpus

• Use of Cells Expressing γ Subunit Variants to Identify Diverse Mechanisms of AMPK Activation (2010, background): “Our study demonstrates that a failure to detect a change in the levels of adenine nucleotides in a cell extract, whether in response to metformin (Fryer et al., 2002; Hawley et al., 2002) or resveratrol (Suchankova et al.”
• Intrasteric control of AMPK via the γ1 subunit AMP allosteric regulatory site (2004, background): “Several drugs, including metformin (Hawley et al. 2002) and rosiglitazone (Fryer et al.”
• Complexes between the LKB1 tumor suppressor, STRADα/β and MO25α/β are upstream kinases in the AMP-activated protein kinase cascade (2003, background): “The drugs AICA riboside and phenformin, which activate AMPK in other cell types via distinct mechanisms [24,27], did not activate AMPK in HeLa cells.”
• Metformin Induces a Dietary Restriction–Like State and the Oxidative Stress Response to Extend C. elegans Healthspan via AMPK, LKB1, and SKN-1 (2010, background): “In mammalian models, metformin and other biguanides activate AMPK in reactions needed for some metformin-associated outcomes [20,21,65].”
• AMPK in Health and Disease. (2009, background): “Since the constitutively active AMPK fragment 1 (1-312) is not activated by the PT1 compound, it is proposed that PT1 acts by reversing the autoinhibition of the AIS (313-335).”
• AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. (2005, background): “, 2002) cause increases in the cellular AMP:ATP ratio, this has not been demonstrated for metformin (Fryer et al., 2002; Hawley et al., 2002).”
• Berberine, a Natural Plant Product, Activates AMP-Activated Protein Kinase With Beneficial Metabolic Effects in Diabetic and Insulin-Resistant States (2006, background): “Conversely, it appears that metformin activates AMPK directly via an ill-defined mechanism (8).”
• LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR‐1 (2004, background): “drug metformin did not affect dephosphorylation of AMPK by protein phosphatase-2C in vitro ( Hawley et al, 2002 ).”
• The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level (2008, background): “Indeed, biguanides do not directly activate AMPK in cell free assays (Hawley et al., 2002), but instead appear to inhibit complex I of the respiratory chain leading to an increase in AMP:ATP ratio (El-Mir et al.”