{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T15:05:10Z","timestamp":1772982310135,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["209198\/Z\/17\/Z"],"award-info":[{"award-number":["209198\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Periods of muscle disuse occur during hospitalization, illness or the recovery from (sports) injury and lead to a rapid loss of muscle mass and the development of insulin resistance. Salbutamol is a fast\u2010acting \u03b22\u2010adrenoreceptor agonist that may improve muscle protein synthesis and insulin sensitivity during experimental muscle disuse and thereby attenuate or preserve muscle mass; however, this has not yet been tested as a standalone intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Effects of salbutamol treatment on muscle metabolism were studied in a randomized controlled trial using a human forearm immobilization model (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200920). Before and after immobilization for 2\u2009days, we measured whole\u2010body glucose disposal, forearm glucose uptake and amino acid kinetics during fasting and hyperinsulinaemic\u2013hyperaminoacidaemic\u2013euglycemic clamp conditions using forearm balance and L\u2010[ring\u2010\n                      <jats:sup>2<\/jats:sup>\n                      H\n                      <jats:sub>5<\/jats:sub>\n                      ]\u2010phenylalanine infusion. Underlying mechanistic effects were studied as well using a complementary murine hindleg immobilization model (2\u2009weeks) using tracer approaches (i.e., deuterated water and\n                      <jats:sup>14<\/jats:sup>\n                      C\u2010labelled phenylalanine) and molecular analyses (e.g., RNA\u2010seq and western blot).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In humans, salbutamol enhanced insulin\u2010stimulated glucose disposal on the whole\u2010body level (+21%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.010) but was unable to ameliorate the immobilization\u2010induced decrease in forearm glucose uptake. Salbutamol decreased the efflux of amino acids from the immobilized forearm, indicating increased muscle protein synthesis and\/or inhibition of breakdown. However, this did not affect the immobilization\u2010induced impairment of amino acid net balance in both postabsorptive (\u2212250%) and clamp conditions (\u2212261%, both\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.031). In agreement, in mice, salbutamol increased cumulative muscle protein synthesis (+0.87%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) but did not result in a net gain of muscle mass upon immobilization due to an accompanying increase in muscle protein turnover (+13%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Molecular analyses revealed immobilization inhibited salbutamol's effects on the muscle transcriptome, specifically the muscle contraction pathway (\u22122.1 normalized enrichment score,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Salbutamol increases muscle mass and glucose uptake, although these effects are limited to active but not inactive muscles. This demonstrates that the mechanism of action and efficacy of \u03b22\u2010adrenoreceptor signalling are hampered upon immobilization, which offers potential for a combined treatment intervention of reintroducing muscle contraction and salbutamol administration to improve muscle mass and clinical outcomes during episodes of physical inactivity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70114","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T08:02:05Z","timestamp":1762416125000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anabolic Effects of Salbutamol Are Lost Upon Immobilization"],"prefix":"10.1002","volume":"16","author":[{"given":"Jelle\u00a0C.\u00a0B.\u00a0C.","family":"de Jong","sequence":"first","affiliation":[{"name":"Department of Metabolic Health Research The Netherlands Organization for Applied Scientific Research (TNO)  Leiden The Netherlands"},{"name":"Human and Animal Physiology Wageningen University  Wageningen The Netherlands"},{"name":"Department of Microbiology and Systems Biology The Netherlands Organization for Applied Scientific Research (TNO)  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom\u00a0S.\u00a0O.","family":"Jameson","sequence":"additional","affiliation":[{"name":"Department of Public Health and Sport Sciences, Faculty of Health and Life Sciences University of Exeter  Exeter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rob\u00a0C.","family":"Andrews","sequence":"additional","affiliation":[{"name":"National Institute for Health and Care Research (NIHR) Exeter Biomedical Research Centre (BRC)  Exeter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mandy\u00a0V.","family":"Dunlop","sequence":"additional","affiliation":[{"name":"Department of Public Health and Sport Sciences, Faculty of Health and Life Sciences University of Exeter  Exeter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doaa\u00a0R.","family":"Abdelrahman","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Texas Medical Branch  Galveston Texas USA"},{"name":"Sealy Center on Aging University of Texas Medical Branch  Galveston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew\u00a0J.","family":"Murton","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Texas Medical Branch  Galveston Texas USA"},{"name":"Sealy Center on Aging University of Texas Medical Branch  Galveston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martien\u00a0P.\u00a0M.","family":"Caspers","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Systems Biology The Netherlands Organization for Applied Scientific Research (TNO)  Leiden The 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Wageningen University  Wageningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Guigas","sequence":"additional","affiliation":[{"name":"Leiden University Center for Infectious Diseases Leiden University Medical Center (LUMC)  Leiden the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"van Duijn","sequence":"additional","affiliation":[{"name":"Department of Metabolic Health Research The Netherlands Organization for Applied Scientific Research (TNO)  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wouter\u00a0H.\u00a0J.","family":"Vaes","sequence":"additional","affiliation":[{"name":"Department of Metabolic Health Research The Netherlands Organization for Applied Scientific Research (TNO)  Leiden The 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