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Ketogenic Diet Regulates Cardiac Remodeling and Calcium Homeostasis in Diabetic Rat Cardiomyopathy
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 (Ca(2+)) homeostasis. We investigated the effects of a KD on Ca(2+) homeostasis and electrophysiology...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10671812/ https://www.ncbi.nlm.nih.gov/pubmed/38003332 http://dx.doi.org/10.3390/ijms242216142 |
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author | Lee, Ting-I Trang, Nguyen Ngoc Lee, Ting-Wei Higa, Satoshi Kao, Yu-Hsun Chen, Yao-Chang Chen, Yi-Jen |
author_facet | Lee, Ting-I Trang, Nguyen Ngoc Lee, Ting-Wei Higa, Satoshi Kao, Yu-Hsun Chen, Yao-Chang Chen, Yi-Jen |
author_sort | Lee, Ting-I |
collection | PubMed |
description | 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 (Ca(2+)) homeostasis. We investigated the effects of a KD on Ca(2+) 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 Ca(2+) 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 Ca(2+) transients, sarcoplasmic reticular Ca(2+) content, sodium (Na(+))-Ca(2+) exchanger currents (reverse mode), L-type Ca(2+) contents, sarcoplasmic reticulum ATPase contents, Cav1.2 contents. Furthermore, these rats exhibited elevated ratios of phosphorylated to total proteins across multiple Ca(2+) 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 Ca(2+) 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 Ca(2+) homeostasis, contributing to its cardioprotection in DM. |
format | Online Article Text |
id | pubmed-10671812 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106718122023-11-09 Ketogenic Diet Regulates Cardiac Remodeling and Calcium Homeostasis in Diabetic Rat Cardiomyopathy Lee, Ting-I Trang, Nguyen Ngoc Lee, Ting-Wei Higa, Satoshi Kao, Yu-Hsun Chen, Yao-Chang Chen, Yi-Jen Int J Mol Sci Article 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 (Ca(2+)) homeostasis. We investigated the effects of a KD on Ca(2+) 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 Ca(2+) 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 Ca(2+) transients, sarcoplasmic reticular Ca(2+) content, sodium (Na(+))-Ca(2+) exchanger currents (reverse mode), L-type Ca(2+) contents, sarcoplasmic reticulum ATPase contents, Cav1.2 contents. Furthermore, these rats exhibited elevated ratios of phosphorylated to total proteins across multiple Ca(2+) 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 Ca(2+) 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 Ca(2+) homeostasis, contributing to its cardioprotection in DM. MDPI 2023-11-09 /pmc/articles/PMC10671812/ /pubmed/38003332 http://dx.doi.org/10.3390/ijms242216142 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lee, Ting-I Trang, Nguyen Ngoc Lee, Ting-Wei Higa, Satoshi Kao, Yu-Hsun Chen, Yao-Chang Chen, Yi-Jen Ketogenic Diet Regulates Cardiac Remodeling and Calcium Homeostasis in Diabetic Rat Cardiomyopathy |
title | Ketogenic Diet Regulates Cardiac Remodeling and Calcium Homeostasis in Diabetic Rat Cardiomyopathy |
title_full | Ketogenic Diet Regulates Cardiac Remodeling and Calcium Homeostasis in Diabetic Rat Cardiomyopathy |
title_fullStr | Ketogenic Diet Regulates Cardiac Remodeling and Calcium Homeostasis in Diabetic Rat Cardiomyopathy |
title_full_unstemmed | Ketogenic Diet Regulates Cardiac Remodeling and Calcium Homeostasis in Diabetic Rat Cardiomyopathy |
title_short | Ketogenic Diet Regulates Cardiac Remodeling and Calcium Homeostasis in Diabetic Rat Cardiomyopathy |
title_sort | ketogenic diet regulates cardiac remodeling and calcium homeostasis in diabetic rat cardiomyopathy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10671812/ https://www.ncbi.nlm.nih.gov/pubmed/38003332 http://dx.doi.org/10.3390/ijms242216142 |
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