{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:49:55Z","timestamp":1792511395310,"version":"4.5.0"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T00:00:00Z","timestamp":1708905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015223","name":"Danish Diabetes and Endocrine Academy","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015223","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010983","name":"Health Research Fund of Central Denmark Region","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010983","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Sodium glucose co\u2010transporter\u20102 (SGLT2) inhibition lowers glucose levels independently of insulin, leading to reduced insulin secretion and increased lipolysis, resulting in elevated circulating free fatty acids (FFAs). While SGLT2 inhibition improves tissue insulin sensitivity, the increase in circulating FFAs could reduce insulin sensitivity in skeletal muscle and the liver. We aimed to investigate the effects of SGLT2 inhibition on substrate utilization in skeletal muscle and the liver and to measure beta\u2010cell function and glucose tolerance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirteen metformin\u2010treated individuals with type 2 diabetes were randomized to once\u2010daily empagliflozin 25\u2009mg or placebo for 4\u2009weeks in a crossover design. Skeletal muscle glucose and FFA uptake together with hepatic tissue FFA uptake were measured using [<jats:sup>18<\/jats:sup>F]FDG positron emission tomography\/computed tomography (PET\/CT) and [<jats:sup>11<\/jats:sup>C]palmitate PET\/CT. Insulin secretion and action were estimated using the oral minimal model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Empagliflozin did not affect glucose (0.73\u2009\u00b1\u20090.30 <jats:italic>vs<\/jats:italic>. 1.16\u2009\u00b1\u20090.64, \u03bcmol\/g\/min <jats:italic>p<\/jats:italic>\u2009=\u20090.11) or FFA <jats:bold>(<\/jats:bold>0.60\u2009\u00b1\u20090.30 <jats:italic>vs<\/jats:italic>. 0.56\u2009\u00b1\u20090.3, \u03bcmol\/g\/min <jats:italic>p<\/jats:italic>\u2009=\u20090.54) uptake in skeletal muscle. FFA uptake in the liver (21.2\u2009\u00b1\u200910.1 <jats:italic>vs<\/jats:italic>. 19\u2009\u00b1\u20098.8, \u03bcmol\/100\u2009ml\/min <jats:italic>p<\/jats:italic>\u2009=\u20090.32) was unaffected.<\/jats:p><jats:p>Empagliflozin increased total beta\u2010cell responsivity (20\u2009\u00b1\u20098 <jats:italic>vs<\/jats:italic>. 14\u2009\u00b1\u20099, 10<jats:sup>\u22129<\/jats:sup>\u00a0min<jats:sup>\u22121<\/jats:sup>, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) and glucose effectiveness (2.6\u2009\u00d7\u200910<jats:sup>\u22122<\/jats:sup>\u2009\u00b1\u20090.3\u2009\u00d7\u200910<jats:sup>\u22122<\/jats:sup> <jats:italic>vs<\/jats:italic>. 2.4\u2009\u00d7\u200910<jats:sup>\u22122<\/jats:sup>\u2009\u00b1\u20090.3\u2009\u00d7\u200910<jats:sup>\u22122<\/jats:sup>, dL\/kg\/min, <jats:italic>p<\/jats:italic>\u2009=\u20090.02).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Despite improved beta\u2010cell function and glucose tolerance, empagliflozin does not appear to affect skeletal muscle FFA or glucose uptake.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcpt.13991","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T04:09:17Z","timestamp":1709006957000},"page":"643-656","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Four weeks SGLT2 inhibition improves beta cell function and glucose tolerance without affecting muscle free fatty acid or glucose uptake in subjects with type 2 diabetes"],"prefix":"10.1111","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4796-9355","authenticated-orcid":false,"given":"Jens Hohw\u00fc","family":"Voigt","sequence":"first","affiliation":[{"name":"Steno Diabetes Center Aarhus  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrine M.","family":"Lauritsen","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Aarhus  Aarhus Denmark"},{"name":"Department of Endocrinology and Internal Medicine Aarhus University Hospital  Aarhus Denmark"},{"name":"Danish Diabetes Academy Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steen B\u00f8nl\u00f8kke","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Aarhus  Aarhus Denmark"},{"name":"Department of Endocrinology and Internal Medicine Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troels K.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Aarhus  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"M\u00f8ller","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Aarhus  Aarhus Denmark"},{"name":"Department of Endocrinology and Internal Medicine Aarhus University Hospital  Aarhus 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