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However, following exercise, high circulating fatty acid (FA) levels might counteract this. We hypothesized that such inhibition would be reduced by forcibly increasing carbohydrate oxidation through pharmacological activation of the pyruvate dehydrogenase complex (PDC). Insulin-stimulated glucose uptake was examined with a crossover design in healthy young men (n = 8) in a previously exercised and a rested leg during a hyperinsulinemic-euglycemic clamp 5 h after one-legged exercise with 1) infusion of saline, 2) infusion of intralipid imitating circulating FA levels during recovery from whole-body exercise, and 3) infusion of intralipid + oral PDC activator, dichloroacetate (DCA). Intralipid infusion reduced insulin-stimulated glucose uptake by 19% in the previously exercised leg, which was not observed in the contralateral rested leg. Interestingly, this effect of intralipid in the exercised leg was abolished by DCA, which increased muscle PDC activity (130%) and flux (acetylcarnitine 130%) and decreased inhibitory phosphorylation of PDC on Ser293 (\u223c40%) and Ser300 (\u223c80%). Novel insight is provided into the regulatory interaction between glucose and lipid metabolism during exercise recovery. Coupling exercise and PDC flux activation upregulated the capacity for both glucose transport (exercise) and oxidation (DCA), which seems necessary to fully stimulate insulin-stimulated glucose uptake during recovery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                  <\/jats:sec>","DOI":"10.2337\/db23-0879","type":"journal-article","created":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T16:50:36Z","timestamp":1712940636000},"page":"1072-1083","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacological Activation of PDC Flux Reverses Lipid-Induced Inhibition of Insulin Action in Muscle During Recovery From Exercise"],"prefix":"10.2337","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9551-5837","authenticated-orcid":false,"given":"Christian S.","family":"Carl","sequence":"first","affiliation":[{"name":"1The August Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie M.","family":"Jensen","sequence":"additional","affiliation":[{"name":"2Clinical Research, Copenhagen University Hospital\u2013Steno Diabetes Center Copenhagen, Herlev, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim A.","family":"Sj\u00f8berg","sequence":"additional","affiliation":[{"name":"1The August Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dumitru","family":"Constantin-Teodosiu","sequence":"additional","affiliation":[{"name":"3David Greenfield Human Physiology Laboratory, National Institute for Health and Care Research Nottingham Biomedical Research Centre, Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, The Medical School, Queen\u2019s Medical Centre, University of Nottingham, Nottingham, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian R.","family":"Hill","sequence":"additional","affiliation":[{"name":"3David Greenfield Human Physiology Laboratory, National Institute for Health and Care Research Nottingham Biomedical Research Centre, Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, The Medical School, Queen\u2019s Medical Centre, University of Nottingham, Nottingham, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rasmus","family":"Kj\u00f8bsted","sequence":"additional","affiliation":[{"name":"1The August Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul L.","family":"Greenhaff","sequence":"additional","affiliation":[{"name":"3David Greenfield Human Physiology Laboratory, National Institute for Health and Care Research Nottingham Biomedical Research Centre, Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, The Medical School, Queen\u2019s Medical Centre, University of Nottingham, Nottingham, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f8rgen F.P.","family":"Wojtaszewski","sequence":"additional","affiliation":[{"name":"1The August Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik A.","family":"Richter","sequence":"additional","affiliation":[{"name":"1The August Krogh Section for Molecular Physiology, Department of Nutrition, 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