{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T19:04:41Z","timestamp":1788289481995,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T00:00:00Z","timestamp":1582761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG CRC 1213"],"award-info":[{"award-number":["DFG CRC 1213"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The cardiac expression of the mitochondrial uncoupling protein (UCP)-2 is increased in patients with heart failure. However, the underlying causes as well as the possible consequences of these alterations during the transition from hypertrophy to heart failure are still unclear. To investigate the role of UCP-2 mechanistically, expression of UCP-2 was silenced by small interfering RNA in adult rat ventricular cardiomyocytes. We demonstrate that a downregulation of UCP-2 by siRNA in cardiomyocytes preserves contractile function in the presence of angiotensin II. Furthermore, silencing of UCP-2 was associated with an upregulation of glucose transporter type (Glut)-4, increased glucose uptake, and reduced intracellular lactate levels, indicating improvement of the oxidative glucose metabolism. To study this adaptation in vivo, spontaneously hypertensive rats served as a model for cardiac hypertrophy due to pressure overload. During compensatory hypertrophy, we found low UCP-2 levels with an upregulation of Glut-4, while the decompensatory state with impaired function was associated with an increase of UCP-2 and reduced Glut-4 expression. By blocking the aldosterone receptor with spironolactone, both cardiac function as well as UCP-2 and Glut-4 expression levels of the compensated phase could be preserved. Furthermore, we were able to confirm this by left ventricular (LV) biopsies of patients with end-stage heart failure. The results of this study show that UCP-2 seems to impact the cardiac glucose metabolism during the transition from hypertrophy to failure by affecting glucose uptake through Glut-4. We suggest that the failing heart could benefit from low UCP-2 levels by improving the efficiency of glucose oxidation. For this reason, UCP-2 inhibition might be a promising therapeutic strategy to prevent the development of heart failure.<\/jats:p>","DOI":"10.3390\/cells9030552","type":"journal-article","created":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T07:35:30Z","timestamp":1583134530000},"page":"552","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Alterations in Glucose Metabolism During the Transition to Heart Failure: The Contribution of UCP-2"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6455-8765","authenticated-orcid":false,"given":"Hanna Sarah","family":"Kutsche","sequence":"first","affiliation":[{"name":"Physiologisches Institut, Justus-Liebig-Universit\u00e4t, 35392 Gie\u00dfen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Schreckenberg","sequence":"additional","affiliation":[{"name":"Physiologisches Institut, Justus-Liebig-Universit\u00e4t, 35392 Gie\u00dfen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Weber","sequence":"additional","affiliation":[{"name":"Physiologisches Institut, Justus-Liebig-Universit\u00e4t, 35392 Gie\u00dfen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Hirschh\u00e4user","sequence":"additional","affiliation":[{"name":"Physiologisches Institut, Justus-Liebig-Universit\u00e4t, 35392 Gie\u00dfen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Rohrbach","sequence":"additional","affiliation":[{"name":"Physiologisches Institut, Justus-Liebig-Universit\u00e4t, 35392 Gie\u00dfen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Li","sequence":"additional","affiliation":[{"name":"Physiologisches Institut, Justus-Liebig-Universit\u00e4t, 35392 Gie\u00dfen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Niemann","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum Gie\u00dfen, Klinik f\u00fcr Herz-, Kinderherz- und Gef\u00e4\u00dfchirurgie, 35392 Gie\u00dfen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Schulz","sequence":"additional","affiliation":[{"name":"Physiologisches Institut, Justus-Liebig-Universit\u00e4t, 35392 Gie\u00dfen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus-Dieter","family":"Schl\u00fcter","sequence":"additional","affiliation":[{"name":"Physiologisches Institut, Justus-Liebig-Universit\u00e4t, 35392 Gie\u00dfen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1093\/eurheartj\/ehw128","article-title":"2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"37","author":"Ponikowski","year":"2016","journal-title":"Eur. 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