Epigenetic effects of metformin: From molecular mechanisms to clinical implications
MetadataShow full item record
There is a growing body of evidence that links epigenetic modifications to type 2 diabetes. Researchers have more recently investigated effects of commonly used medications, including those prescribed for diabetes, on epigenetic processes. This work reviews the influence of the widely used antidiabetic drug metformin on epigenomics, microRNA levels and subsequent gene expression, and potential clinical implications. Metformin may influence the activity of numerous epigenetic modifying enzymes, mostly by modulating the activation of AMP-activated protein kinase (AMPK). Activated AMPK can phosphorylate numerous substrates, including epigenetic enzymes such as histone acetyltransferases (HATs), class II histone deacetylases (HDACs) and DNA methyltransferases (DNMTs), usually resulting in their inhibition; however, HAT1 activity may be increased. Metformin has also been reported to decrease expression of multiple histone methyltransferases, to increase the activity of the class III HDAC SIRT1 and to decrease the influence of DNMT inhibitors. There is evidence that these alterations influence the epigenome and gene expression, and may contribute to the antidiabetic properties of metformin and, potentially, may protect against cancer, cardiovascular disease, cognitive decline and aging. The expression levels of numerous microRNAs are also reportedly influenced by metformin treatment and may confer antidiabetic and anticancer activities. However, as the reported effects of metformin on epigenetic enzymes act to both increase and decrease histone acetylation, histone and DNA methylation, and gene expression, a significant degree of uncertainty exists concerning the overall effect of metformin on the epigenome, on gene expression, and on the subsequent effect on the health of metformin users.
This is the peer reviewed version of the following article: Bridgeman, S. and Ellison, G. and Melton, P. and Newsholme, P. and Mamotte, C. 2018. Epigenetic effects of metformin: From molecular mechanisms to clinical implications. Diabetes, Obesity and Metabolism. 20 (7): pp. 1553-1562, which has been published in final form at 10.1111/dom.13262. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving at http://olabout.wiley.com/WileyCDA/Section/id-828039.html
Showing items related by title, author, creator and subject.
Allen, S.; Mamotte, Cyril (2017)Statins are widely used to prevent major cardiovascular events by lowering serum cholesterol. There is evidence that statins have pleiotropic effects-that is, cholesterol-independent effects-that may also confer protection ...
Epigenetic demthylation of sFRPs, with emphasis on sFRP4 activation, leading to Wnt signalling suppression and histone modifications in breast, prostate, and ovary cancer stem cells.Deshmukh, A.; Arfuso, F.; Newsholme, P.; Dharmarajan, Arunasalam (2019)The expression and levels of secreted frizzled-related proteins (sFRPs), important Wnt signalling antagonists, have been reported to be reduced in various cancers, and are associated with disease progression and poor ...
Involvement of the Histone Acetyltransferase AtHAC1 in the Regulation of Flowering Time via Repression of FLOWERING LOCUS C in Arabidopsis1[W][OA]Deng, Weiwei; Liu, C.Y.; Deng, X.; Niu, L.; Cao, X.F. (2007)Histone acetylation is an important posttranslational modification correlated with gene activation. In Arabidopsis (Arabidopsis thaliana), the histone acetyltransferase AtHAC1 is homologous to animal p300/CREB (cAMP-responsive ...