{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T19:37:47Z","timestamp":1793216267611,"version":"4.5.0"},"reference-count":43,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T00:00:00Z","timestamp":1624579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003086","name":"Eusko Jaurlaritza","doi-asserted-by":"publisher","award":["PIBA2018-58"],"award-info":[{"award-number":["PIBA2018-58"]}],"id":[{"id":"10.13039\/501100003086","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003086","name":"Eusko Jaurlaritza","doi-asserted-by":"publisher","award":["GIC18\/150"],"award-info":[{"award-number":["GIC18\/150"]}],"id":[{"id":"10.13039\/501100003086","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000921","name":"European Cooperation in Science and Technology","doi-asserted-by":"publisher","award":["CA16225"],"award-info":[{"award-number":["CA16225"]}],"id":[{"id":"10.13039\/501100000921","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Diabetic patients have prolonged cardiac repolarization and higher risk of arrhythmia. Besides, diabetes activates the innate immune system, resulting in higher levels of plasmatic cytokines, which are described to prolong ventricular repolarization. Methods: We characterize a metabolic model of type 2 diabetes (T2D) with prolonged cardiac repolarization. Sprague-Dawley rats were fed on a high-fat diet (45% Kcal from fat) for 6 weeks, and a low dose of streptozotozin intraperitoneally injected at week 2. Body weight and fasting blood glucose were measured and electrocardiograms of conscious animals were recorded weekly. Plasmatic lipid profile, insulin, cytokines, and arrhythmia susceptibility were determined at the end of the experimental period. Outward K+ currents and action potentials were recorded in isolated ventricular myocytes by patch-clamp. Results: T2D animals showed insulin resistance, hyperglycemia, and elevated levels of plasma cholesterol, triglycerides, TNF\u03b1, and IL-1b. They also developed bradycardia and prolonged QTc-interval duration that resulted in increased susceptibility to severe ventricular tachycardia under cardiac challenge. Action potential duration (APD) was prolonged in control cardiomyocytes incubated 24 h with plasma isolated from diabetic rats. However, adding TNF\u03b1 and IL-1b receptor blockers to the serum of diabetic animals prevented the increased APD. Conclusions: The elevation of the circulating levels of TNF\u03b1 and IL-1b are responsible for impaired ventricular repolarization and higher susceptibility to cardiac arrhythmia in our metabolic model of T2D.<\/jats:p>","DOI":"10.3390\/ijms22136827","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T04:46:57Z","timestamp":1624596417000},"page":"6827","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Molecular and Electrophysiological Role of Diabetes-Associated Circulating Inflammatory Factors in Cardiac Arrhythmia Remodeling in a Metabolic-Induced Model of Type 2 Diabetic Rat"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6560-3035","authenticated-orcid":false,"given":"Julian","family":"Zayas-Arrabal","sequence":"first","affiliation":[{"name":"Departament of Physiology, Facultad de Farmacia, Universidad del Pa\u00eds Vasco UPV\/EHU, 01006 Vitoria-Gasteiz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaia","family":"Alquiza","sequence":"additional","affiliation":[{"name":"Departament of Physiology, Facultad de Farmacia, Universidad del Pa\u00eds Vasco UPV\/EHU, 01006 Vitoria-Gasteiz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6675-2534","authenticated-orcid":false,"given":"Erkan","family":"Tuncay","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine, Ankara University, 06100 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belma","family":"Turan","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine, Lokman Hekim University, 06510 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Gallego","sequence":"additional","affiliation":[{"name":"Departament of Physiology, Facultad de Farmacia, Universidad del Pa\u00eds Vasco UPV\/EHU, 01006 Vitoria-Gasteiz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6219-3317","authenticated-orcid":false,"given":"Oscar","family":"Casis","sequence":"additional","affiliation":[{"name":"Departament of Physiology, Facultad de Farmacia, Universidad del Pa\u00eds Vasco UPV\/EHU, 01006 Vitoria-Gasteiz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s11892-004-0022-8","article-title":"Sudden cardiac death in patients with diabetes","volume":"4","author":"McFarlane","year":"2004","journal-title":"Curr. 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