Metformin is currently the first-line treatment option for patients with type 2 diabetes mellitus, yet its mechanism of action remains uncertain. A new study reveals the important role for the activation of a duodenal AMPK-dependent neuronal pathway in the acute antihyperglycaemic effect of metformin and the inhibition of hepatic glucose production.
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References
American Diabetes Association. Standards of medical care in diabetes—2014. Diabetes Care 37 (Suppl. 1), S14–S80 (2014).
Foretz, M., Guigas, B., Bertrand, L., Pollak, M. & Viollet, B. Metformin: from mechanisms of action to therapies. Cell Metab. 20, 953–966 (2014).
Foretz, M. et al. Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state. J. Clin. Invest. 120, 2355–2369 (2010).
Miller, R. A. et al. Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP. Nature 494, 256–260 (2013).
Madiraju, A. K. et al. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature 510, 542–546 (2014).
Bailey, C. J., Wilcock, C. & Scarpello, J. H. Metformin and the intestine. Diabetologia 51, 1552–1553 (2008).
Duca, F. A. et al. Metformin activates a duodenal Ampk-dependent pathway to lower hepatic glucose production in rats. Nat. Med. 21, 506–511 (2015).
Maida, A., Lamont, B. J., Cao, X. & Drucker, D. J. Metformin regulates the incretin receptor axis via a pathway dependent on peroxisome proliferator-activated receptor-α in mice. Diabetologia 54, 339–349 (2011).
Napolitano, A. et al. Novel gut-based pharmacology of metformin in patients with type 2 diabetes mellitus. PLoS ONE 9, e100778 (2014).
Côté, C. D. et al. Resveratrol activates duodenal Sirt1 to reverse insulin resistance in rats through a neuronal network. Nat. Med. 21, 498–505 (2015).
Acknowledgements
The authors acknowledge funding from INSERM, CNRS, Université Paris Descartes, Agence Nationale de la Recherche, Société Francophone du Diabète, Région Ile de France, Association pour la Recherche sur le Diabète and the Département Hospitalo-Universitaire (DHU) AUToimmune and HORmonal diseaseS.
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Foretz, M., Viollet, B. Metformin takes a new route to clinical efficacy. Nat Rev Endocrinol 11, 390–392 (2015). https://doi.org/10.1038/nrendo.2015.85
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DOI: https://doi.org/10.1038/nrendo.2015.85
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