{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T02:25:24Z","timestamp":1784082324274,"version":"3.55.0"},"reference-count":40,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T00:00:00Z","timestamp":1656460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>An oversupply of nutrients with a loss of metabolic flexibility and subsequent cardiac dysfunction are hallmarks of diabetic cardiomyopathy. Even if excess substrate is offered, the heart suffers energy depletion as metabolic fluxes are diminished. To study the effects of a high glucose supply, a stably glucose transporter type 4 (GLUT4)-overexpressing cell line presenting an onset of diabetic cardiomyopathy-like phenotype was established. Long-term hyperglycaemia effects were analysed. Rat cardiomyoblasts overexpressing GLUT4 (H9C2KE2) were cultured under normo- and hyperglycaemic conditions for long-term. Expression profiles of several proteins were compared to non-transfected H9C2 cells (H9C2) using RT-qPCR, proteomics-based analysis, or Western blotting. GLUT4 surface analysis, glucose uptake, and cell morphology changes as well as apoptosis\/necrosis measurements were performed using flow cytometry. Additionally, brain natriuretic peptide (BNP) levels, reactive oxygen species (ROS) formation, glucose consumption, and lactate production were quantified. Long-term hyperglycaemia in H9C2KE2 cells induced increased GLUT4 presence on the cell surface and was associated with exaggerated glucose influx and lactate production. On the metabolic level, hyperglycaemia affected the tricarboxylic acid (TCA) cycle with accumulation of fumarate. This was associated with increased BNP-levels, oxidative stress, and lower antioxidant response, resulting in pronounced apoptosis and necrosis. Chronic glucose overload in cardiomyoblasts induced by GLUT4 overexpression and hyperglycaemia resulted in metabolically stimulated proteome profile changes and metabolic alterations on the TCA level.<\/jats:p>","DOI":"10.3390\/ijms23137255","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T22:43:28Z","timestamp":1656542608000},"page":"7255","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Chronic Hyperglycaemia Inhibits Tricarboxylic Acid Cycle in Rat Cardiomyoblasts Overexpressing Glucose Transporter Type 4"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5777-3715","authenticated-orcid":false,"given":"Bernd","family":"Stratmann","sequence":"first","affiliation":[{"name":"Herz- and Diabeteszentrum NRW, Diabeteszentrum, Ruhr Universit\u00e4t Bochum, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6553-4631","authenticated-orcid":false,"given":"Britta","family":"Eggers","sequence":"additional","affiliation":[{"name":"Medizinisches Proteom-Center, Centre for Translational and Behavioural Neurosciences, Medical Faculty, Ruhr-University Bochum, 44801 Bochum, Germany"},{"name":"Medical Proteome Analysis, Centre for Protein Diagnostics (PRODI), Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Mattern","sequence":"additional","affiliation":[{"name":"Herz- and Diabeteszentrum NRW, Diabeteszentrum, Ruhr Universit\u00e4t Bochum, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tayana","family":"Silva de Carvalho","sequence":"additional","affiliation":[{"name":"Herz- and Diabeteszentrum NRW, Diabeteszentrum, Ruhr Universit\u00e4t Bochum, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3313-8845","authenticated-orcid":false,"given":"Katrin","family":"Marcus","sequence":"additional","affiliation":[{"name":"Medizinisches Proteom-Center, Centre for Translational and Behavioural Neurosciences, Medical Faculty, Ruhr-University Bochum, 44801 Bochum, Germany"},{"name":"Medical Proteome Analysis, Centre for Protein Diagnostics (PRODI), Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diethelm","family":"Tschoepe","sequence":"additional","affiliation":[{"name":"Herz- and Diabeteszentrum NRW, Diabeteszentrum, Ruhr Universit\u00e4t Bochum, 32545 Bad Oeynhausen, Germany"},{"name":"Stiftung DHD (Der herzkranke Diabetiker) Stiftung in der Deutschen Diabetes-Stiftung, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/0002-9149(72)90595-4","article-title":"New Type of Cardiomyopathy Associated with Diabetic Glomeruloscierosis","volume":"30","author":"Rubler","year":"1972","journal-title":"Am. 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