{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:39:09Z","timestamp":1792611549316,"version":"4.5.0"},"reference-count":321,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"MRC","doi-asserted-by":"publisher","award":["MR\/X00533X\/1"],"award-info":[{"award-number":["MR\/X00533X\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"MRC","doi-asserted-by":"publisher","award":["PG\/18\/29\/33731"],"award-info":[{"award-number":["PG\/18\/29\/33731"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"MRC","doi-asserted-by":"publisher","award":["PG\/24\/11961"],"award-info":[{"award-number":["PG\/24\/11961"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["MR\/X00533X\/1"],"award-info":[{"award-number":["MR\/X00533X\/1"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/18\/29\/33731"],"award-info":[{"award-number":["PG\/18\/29\/33731"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/24\/11961"],"award-info":[{"award-number":["PG\/24\/11961"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The growing prevalence of diabetes highlights the urgent need to study diabetic cardiovascular complications, specifically diabetic cardiomyopathy, which is a diabetes-induced myocardial dysfunction independent of hypertension or coronary artery disease. This review examines the role of mitochondrial dysfunction in promoting diabetic cardiac dysfunction and highlights metabolic mechanisms such as hyperglycaemia-induced oxidative stress. Chronic hyperglycaemia and insulin resistance can activate harmful pathways, including advanced glycation end-products (AGEs), protein kinase C (PKC) and hexosamine signalling, uncontrolled reactive oxygen species (ROS) production and mishandling of Ca2+ transient. These processes lead to cardiomyocyte apoptosis, fibrosis and contractile dysfunction. Moreover, endoplasmic reticulum (ER) stress and dysregulated RNA-binding proteins (RBPs) and extracellular vesicles (EVs) contribute to tissue damage, which drives cardiac function towards heart failure (HF). Advanced patient-derived induced pluripotent stem cell (iPSC) cardiac organoids (iPS-COs) are transformative tools for modelling diabetic cardiomyopathy and capturing human disease\u2019s genetic, epigenetic and metabolic hallmarks. iPS-COs may facilitate the precise examination of molecular pathways and therapeutic interventions. Future research directions encourage the integration of advanced models with mechanistic techniques to promote novel therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms26073016","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T06:58:43Z","timestamp":1742972323000},"page":"3016","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Metabolic and Mitochondrial Dysregulations in Diabetic Cardiac Complications"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6343-1864","authenticated-orcid":false,"given":"Asim J.","family":"Tashkandi","sequence":"first","affiliation":[{"name":"Wellcome Wolfson Institute of Experimental Medicine, Queens University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Gorman","sequence":"additional","affiliation":[{"name":"Wellcome Wolfson Institute of Experimental Medicine, Queens University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"McGoldrick Mathers","sequence":"additional","affiliation":[{"name":"Wellcome Wolfson Institute of Experimental Medicine, Queens University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garrett","family":"Carney","sequence":"additional","affiliation":[{"name":"Wellcome Wolfson Institute of Experimental Medicine, Queens University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8780-3484","authenticated-orcid":false,"given":"Andrew","family":"Yacoub","sequence":"additional","affiliation":[{"name":"Wellcome Wolfson Institute of Experimental Medicine, Queens University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4334-5012","authenticated-orcid":false,"given":"Wiwit Ananda Wahyu","family":"Setyaningsih","sequence":"additional","affiliation":[{"name":"Wellcome Wolfson Institute of Experimental Medicine, Queens University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Refik","family":"Kuburas","sequence":"additional","affiliation":[{"name":"Wellcome Wolfson Institute of Experimental Medicine, Queens University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9303-8371","authenticated-orcid":false,"given":"Andriana","family":"Margariti","sequence":"additional","affiliation":[{"name":"Wellcome Wolfson Institute of Experimental Medicine, Queens University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.diabres.2013.11.002","article-title":"Global estimates of diabetes prevalence for 2013 and projections for 2035","volume":"103","author":"Guariguata","year":"2014","journal-title":"Diabetes Res. 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