Our current efforts are aimed at deciphering the function of AMP-activated protein kinase (AMPK) in the gastrointestinal tract and the skeletal muscle as well as exploring the role of Salt-Inducble Kinase (SIK) in the regulation of hepatic glucose production. Our research is devoted to assess their utility in diagnosis and efficacy in therapeutics for type 2 diabetes and obesity. The impact of our research will be relevant not only for the purpose of growing scientific knowledge but also for its translation into new therapeutic strategies. Our research strategy is to discover the key cellular processes governed by AMPK and SIK by using tissue-specific knockout mouse models and genetically modified cell lines with the CRISPR-Cas9 technology; our general objective is to identify and validate target proteins and genes by molecularly interrogating established in vivo and in vitro experimental models (through multi-omics analysis), and to propose specific therapeutic approaches by genetic and pharmacological means.
Main Publications
Foretz M, Guigas B, Viollet B. Metformin: update on mechanisms of action and repurposing potential. Nat Rev Endocrinol. 2023 May 2:1-17. doi: 10.1038/s41574-023-00833-4. PMID: 37130947
Olivier S, Pochard C, Diounou H, Castillo V, Divoux J, Alcantara J, Leclerc J, Guilmeau S, Huet C, Charifi W, Varin TV, Daniel N, Foretz M, Neunlist M, Salomon BL, Ghosh P, Marette A, Rolli-Derkinderen M, Viollet B. Deletion of intestinal epithelial AMP-activated protein kinase alters distal colon permeability but not glucose homeostasis. Mol Metab. 2021 May;47:101183. doi: 10.1016/j.molmet.2021.101183. Epub 2021 Feb 4. PMID: 33548500
Lantier L, Williams AS, Williams IM, Guerin A, Bracy DP, Goelzer M, Foretz M, Viollet B, Hughey CC, Wasserman DH. Reciprocity Between Skeletal Muscle AMPK Deletion and Insulin Action in Diet-Induced Obese Mice. Diabetes. 2020 Aug;69(8):1636-1649. doi: 10.2337/db19-1074. Epub 2020 May 21. PMID: 32439824
Huet C, Boudaba N, Guigas B, Viollet B, Foretz M. Glucose availability but not changes in pancreatic hormones sensitizes hepatic AMPK activity during nutritional transition in rodents. J Biol Chem. 2020 May 1;295(18):5836-5849. doi: 10.1074/jbc.RA119.010244. Epub 2020 Mar 17. PMID: 32184359
Boudaba N, Marion A, Huet C, Pierre R, Viollet B, Foretz M. EBioMedicine. AMPK Re-Activation Suppresses Hepatic Steatosis but its Downregulation Does Not Promote Fatty Liver Development. 2018 Feb;28:194-209. doi: 10.1016/j.ebiom.2018.01.008. Epub 2018 Jan 9. PMID: 29343420
Keywords
AMPK, SIK, diabetes, metabolism, animal models
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ORCID: orcid.org/0000-0002-0121-0224