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Okinawa","award":["111-2314-B-038-106-MY3"],"award-info":[{"award-number":["111-2314-B-038-106-MY3"]}]},{"name":"Foundation for the Development of Internal Medicine in Okinawa","award":["4-02-003"],"award-info":[{"award-number":["4-02-003"]}]},{"name":"Foundation for the Development of Internal Medicine in Okinawa","award":["4-02-006"],"award-info":[{"award-number":["4-02-006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A ketogenic diet (KD) might alleviate patients with diabetic cardiomyopathy. However, the underlying mechanism remains unclear. Myocardial function and arrhythmogenesis are closely linked to calcium (Ca2+) homeostasis. We investigated the effects of a KD on Ca2+ homeostasis and electrophysiology in diabetic cardiomyopathy. Male Wistar rats were created to have diabetes mellitus (DM) using streptozotocin (65 mg\/kg, intraperitoneally), and subsequently treated for 6 weeks with either a normal diet (ND) or a KD. Our electrophysiological and Western blot analyses assessed myocardial Ca2+ homeostasis in ventricular preparations in vivo. Unlike those on the KD, DM rats treated with an ND exhibited a prolonged QTc interval and action potential duration. Compared to the control and DM rats on the KD, DM rats treated with an ND also showed lower intracellular Ca2+ transients, sarcoplasmic reticular Ca2+ content, sodium (Na+)-Ca2+ exchanger currents (reverse mode), L-type Ca2+ contents, sarcoplasmic reticulum ATPase contents, Cav1.2 contents. Furthermore, these rats exhibited elevated ratios of phosphorylated to total proteins across multiple Ca2+ handling proteins, including ryanodine receptor 2 (RyR2) at serine 2808, phospholamban (PLB)-Ser16, and calmodulin-dependent protein kinase II (CaMKII). Additionally, DM rats treated with an ND demonstrated a higher frequency and incidence of Ca2+ leak, cytosolic reactive oxygen species, Na+\/hydrogen-exchanger currents, and late Na+ currents than the control and DM rats on the KD. KD treatment may attenuate the effects of DM-dysregulated Na+ and Ca2+ homeostasis, contributing to its cardioprotection in DM.<\/jats:p>","DOI":"10.3390\/ijms242216142","type":"journal-article","created":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T10:19:27Z","timestamp":1699525167000},"page":"16142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Ketogenic Diet Regulates Cardiac Remodeling and Calcium Homeostasis in Diabetic Rat Cardiomyopathy"],"prefix":"10.3390","volume":"24","author":[{"given":"Ting-I","family":"Lee","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5965-5381","authenticated-orcid":false,"given":"Nguyen Ngoc","family":"Trang","sequence":"additional","affiliation":[{"name":"Radiology Center, Bach Mai Hospital, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7058-2868","authenticated-orcid":false,"given":"Ting-Wei","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5735-6249","authenticated-orcid":false,"given":"Satoshi","family":"Higa","sequence":"additional","affiliation":[{"name":"Cardiac Electrophysiology and Pacing Laboratory, Division of Cardiovascular Medicine, Makiminato Central Hospital, Makiminato Urasoe City, Okinawa 901-2131, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8687-5091","authenticated-orcid":false,"given":"Yu-Hsun","family":"Kao","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-Chang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7224-4491","authenticated-orcid":false,"given":"Yi-Jen","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Cardiovascular Research Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1007\/s11940-008-0043-8","article-title":"The ketogenic diet: Uses in epilepsy and other neurologic illnesses","volume":"10","author":"Baranano","year":"2008","journal-title":"Curr. 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