{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T07:27:49Z","timestamp":1784618869493,"version":"3.55.0"},"reference-count":41,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,6,11]]},"abstract":"<jats:p>\n                    Liraglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist used for the treatment of T2D, has been shown to alleviate diabetic cardiomyopathy (DbCM) in experimental T2D, which was associated with increased myocardial glucose oxidation. To determine whether this increase in glucose oxidation is necessary for cardioprotection, we hypothesized that liraglutide\u2019s ability to alleviate DbCM would be abolished in mice with cardiomyocyte-specific deletion of pyruvate dehydrogenase (PDH;\n                    <jats:italic>Pdha1<\/jats:italic>\n                    <jats:sup>CM\u2212\/\u2212<\/jats:sup>\n                    mice), the rate-limiting enzyme of glucose oxidation. Male\n                    <jats:italic>Pdha1<\/jats:italic>\n                    <jats:sup>CM\u2212\/\u2212<\/jats:sup>\n                    mice and their \u03b1-myosin heavy chain Cre expressing littermates (\u03b1MHC\n                    <jats:sup>Cre<\/jats:sup>\n                    mice) were subjected to experimental T2D via 10 weeks of high-fat diet supplementation, with a single low-dose injection of streptozotocin (75 mg\/kg) provided at week 4. All mice were randomized to treatment with either vehicle control or liraglutide (30 \u00b5g\/kg) twice daily during the final 2.5 weeks, with cardiac function assessed via ultrasound echocardiography. As expected, liraglutide treatment improved glucose homeostasis in both \u03b1MHC\n                    <jats:sup>Cre<\/jats:sup>\n                    and\n                    <jats:italic>Pdha1<\/jats:italic>\n                    <jats:sup>CM\u2212\/\u2212<\/jats:sup>\n                    mice with T2D, in the presence of mild weight loss. Parameters of systolic function were unaffected by liraglutide treatment in both \u03b1MHC\n                    <jats:sup>Cre<\/jats:sup>\n                    and\n                    <jats:italic>Pdha1<\/jats:italic>\n                    <jats:sup>CM\u2212\/\u2212<\/jats:sup>\n                    mice with T2D. However, liraglutide treatment alleviated diastolic dysfunction in \u03b1MHC\n                    <jats:sup>Cre<\/jats:sup>\n                    mice, as indicated by an increase and decrease in the e\u2032\/a\u2032 and E\/e\u2032 ratios, respectively. Conversely, liraglutide failed to rescue these indices of diastolic dysfunction in\n                    <jats:italic>Pdha1<\/jats:italic>\n                    <jats:sup>CM\u2212\/\u2212<\/jats:sup>\n                    mice. Our findings suggest that increases in glucose oxidation are necessary for GLP-1R agonist mediated alleviation of DbCM. As such, strategies aimed at increasing PDH activity may represent a novel approach for the treatment of DbCM.\n                  <\/jats:p>","DOI":"10.1530\/joe-24-0032","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T06:34:08Z","timestamp":1718087648000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":11,"title":["Liraglutide alleviates experimental diabetic cardiomyopathy in a PDH-dependent manner"],"prefix":"10.1530","volume":"262","author":[{"given":"Jordan S F","family":"Chan","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda A","family":"Greenwell","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina T","family":"Saed","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus J","family":"Stenlund","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indiresh A","family":"Mangra-Bala","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Amirhossein","family":"Tabatabaei Dakhili","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5586-5875","authenticated-orcid":true,"given":"Kunyan","family":"Yang","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally R","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farah","family":"Eaton","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keshav","family":"Gopal","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9574-5707","authenticated-orcid":true,"given":"John R","family":"Ussher","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Canadian Journal of Cardiology","first-page":"140","article-title":"The GLP-1 receptor agonist liraglutide increases myocardial glucose oxidation rates via indirect mechanisms and mitigates experimental diabetic cardiomyopathy","volume":"37","author":"Almutairi","year":"2021","unstructured":"Almutairi MGopal KGreenwell AAYoung AGill RAburasayn HAl Batran RChahade JJGandhi MEaton 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