Physiopathology of AMPK and AMPK-related protein kinase in diabetes and obesity

Our work is dedicated to the understanding of the critical roles of AMP-activated protein kinase (AMPK) and salt inducible kinase (SIK), member of the AMPK-related protein kinase family, in various physiopathological conditions from diabetes to obesity, and to assess their utility in diagnosis and efficacy in therapeutics.

PI : Benoit Viollet

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. Our current efforts are aimed at deciphering the function of AMPK in gastrointestinal tract and skeletal muscle as well as exploring the role of SIK in the regulation of hepatic glucose production. 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.

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

Team members

A new article from Cécile Haumaitre and collaborators discusses the origin of pancreatic lesions associated with pancreatic cancer

Diabetes Institute, From inflammation to cancer in digestive diseases, Publications

Pancreatic ductal adenocarcinoma is currently the fourth leading cause of cancer death worldwide. It is projected to become the second leading cause of cancer death by 2030. Unfortunately, PDAC is often diagnosed at an advanced stage, resulting in a 5-year survival rate of less than 10%. Since the most common precancerous lesions of PDAC are currently not clinically detectable, understanding the mechanisms that lead to their formation and progression is crucial to enabling early diagnosis and more effective therapeutic intervention.