{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:48:09Z","timestamp":1791290889143,"version":"4.3.0"},"reference-count":53,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,6,15]]},"abstract":"<jats:p>AMPK (AMP-activated protein kinase) is an attractive therapeutic drug target for treating metabolic disorders. We studied the effects of an AMPK activator developed by Merck (ex229 from patent application WO2010036613), comparing chemical activation with contraction in intact incubated skeletal muscles. We also compared effects of ex229 with those of the Abbott A769662 compound and AICAR (5-amino-4-imidazolecarboxamide riboside). In rat epitrochlearis muscle, ex229 dose-dependently increased AMPK activity of \u03b11-, \u03b12-, \u03b21- and \u03b22-containing complexes with significant increases in AMPK activity seen at a concentration of 50\u00a0\u03bcM. At a concentration of 100\u00a0\u03bcM, AMPK activation was similar to that observed after contraction and importantly led to an ~2-fold increase in glucose uptake. In AMPK \u03b11-\/\u03b12-catalytic subunit double-knockout myotubes incubated with ex229, the increases in glucose uptake and ACC (acetyl-CoA carboxylase) phosphorylation seen in control cells were completely abolished, suggesting that the effects of the compound were AMPK-dependent. When muscle glycogen levels were reduced by ~50% after starvation, ex229-induced AMPK activation and glucose uptake were amplified in a wortmannin-independent manner. In L6 myotubes incubated with ex229, fatty acid oxidation was increased. Furthermore, in mouse EDL (extensor digitorum longus) and soleus muscles, ex229 increased both AMPK activity and glucose uptake at least 2-fold. In summary, ex229 efficiently activated skeletal muscle AMPK and elicited metabolic effects in muscle appropriate for treating Type\u00a02 diabetes by stimulating glucose uptake and increasing fatty acid oxidation.<\/jats:p>","DOI":"10.1042\/bj20131673","type":"journal-article","created":{"date-parts":[[2014,3,26]],"date-time":"2014-03-26T06:04:43Z","timestamp":1395813883000},"page":"363-375","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":90,"title":["A small-molecule benzimidazole derivative that potently activates AMPK to increase glucose transport in skeletal muscle: comparison with effects of contraction and other AMPK activators"],"prefix":"10.1042","volume":"460","author":[{"given":"Yu-Chiang","family":"Lai","sequence":"first","affiliation":[{"name":"Universit\u00e9 catholique de Louvain and de Duve Institute, Avenue Hippocrate 75, bte B1.74.02, B-1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samanta","family":"Kviklyte","sequence":"additional","affiliation":[{"name":"Universit\u00e9 catholique de Louvain and de Duve Institute, Avenue Hippocrate 75, bte B1.74.02, B-1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Vertommen","sequence":"additional","affiliation":[{"name":"Universit\u00e9 catholique de Louvain and de Duve Institute, Avenue Hippocrate 75, bte B1.74.02, B-1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Lantier","sequence":"additional","affiliation":[{"name":"INSERM U1016, Institut Cochin, Paris, France"},{"name":"CNRS UMR8104, Paris, France"},{"name":"Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9, Paris 75014, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Foretz","sequence":"additional","affiliation":[{"name":"INSERM U1016, Institut Cochin, Paris, France"},{"name":"CNRS UMR8104, Paris, France"},{"name":"Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9, Paris 75014, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beno\u00eet","family":"Viollet","sequence":"additional","affiliation":[{"name":"INSERM U1016, Institut Cochin, Paris, France"},{"name":"CNRS UMR8104, Paris, France"},{"name":"Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9, Paris 75014, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Hall\u00e9n","sequence":"additional","affiliation":[{"name":"AstraZeneca Research and Development, SE-431 83 M\u00f6lndal, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark\u00a0H.","family":"Rider","sequence":"additional","affiliation":[{"name":"Universit\u00e9 catholique de Louvain and de Duve Institute, Avenue Hippocrate 75, bte B1.74.02, B-1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2014,5,29]]},"reference":[{"key":"2021112215554786000_B1","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/nrm3311","article-title":"AMPK: a nutrient and energy sensor that maintains energy homeostasis","volume":"13","author":"Hardie","year":"2012","journal-title":"Nat. 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