{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:42:27Z","timestamp":1787240547977,"version":"build-2736575974"},"reference-count":44,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T00:00:00Z","timestamp":1597968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 GM-126061  R01GM-132149"],"award-info":[{"award-number":["R01 GM-126061  R01GM-132149"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["17EIA33400063"],"award-info":[{"award-number":["17EIA33400063"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["18PRE34030123"],"award-info":[{"award-number":["18PRE34030123"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cardiac cells can adapt to pathological stress-induced energy crisis by shifting from fatty acid oxidation to glycolysis. However, the use of glucose-insulin-potassium (GIK) solution in patients undergoing cardiac surgery does not alleviate ischemia\/reperfusion (I\/R)-induced energy shortage. This indicates that insulin-mediated translocation of glucose transporter-4 (Glut-4) is impaired in ischemic hearts. Indeed, cardiac myocytes contain two intracellular populations of Glut-4: an insulin-dependent non-endosomal pool (also referred to as Glut-4 storage vesicles, GSVs) and an insulin-independent endosomal pool. Tumor susceptibility gene 101 (Tsg101) has been implicated in the endosomal recycling of membrane proteins. In this study, we aimed to examine whether Tsg101 regulated the sorting and re-distribution of Glut-4 to the sarcolemma membrane of cardiomyocytes under basal and ischemic conditions, using gain- and loss-of-function approaches. Forced overexpression of Tsg101 in mouse hearts and isolated cardiomyocytes could promote Glut-4 re-distribution to the sarcolemma, leading to enhanced glucose entry and adenosine triphosphate (ATP) generation in I\/R hearts which in turn, attenuation of I\/R-induced cardiac dysfunction. Conversely, knockdown of Tsg101 in cardiac myocytes exhibited opposite effects. Mechanistically, we identified that Tsg101 could interact and co-localize with Glut-4 in the sarcolemma membrane of cardiomyocytes. Our findings define Tsg101 as a novel regulator of cardiac Glut-4 trafficking, which may provide a new therapeutic strategy for the treatment of ischemic heart disease.<\/jats:p>","DOI":"10.3390\/cells9091936","type":"journal-article","created":{"date-parts":[[2020,8,23]],"date-time":"2020-08-23T21:28:06Z","timestamp":1598218086000},"page":"1936","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Tsg101 Is Involved in the Sorting and Re-Distribution of Glucose Transporter-4 to the Sarcolemma Membrane of Cardiac Myocytes"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8088-4082","authenticated-orcid":false,"given":"Kobina","family":"Essandoh","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2727-2722","authenticated-orcid":false,"given":"Shan","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"},{"name":"Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"},{"name":"Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingjiang","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianqing","family":"Peng","sequence":"additional","affiliation":[{"name":"Critical Illness Research, Lawson Health Research Institute, London, ON N6A 4G5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0439-8277","authenticated-orcid":false,"given":"Guo-Chang","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,21]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Adjuvant Cardioprotection in Cardiac Surgery: Update","volume":"2014","author":"Wagner","year":"2014","journal-title":"BioMed Res. 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