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Abdurrachim 2017 Cardiovasc Res
Additional label Labels  + , 2017-11  +
Coupling states LEAK  + , OXPHOS  + , ET  +
Diseases Diabetes  +
Has abstract Heart failure is associated with altered m
Heart failure is associated with altered myocardial substrate metabolism and impaired cardiac energetics. Comorbidities like diabetes may influence the metabolic adaptations during heart failure development. We quantified to what extent changes in substrate preference, lipid accumulation, and energy status predict the longitudinal development of hypertrophy and failure in the non-diabetic and the diabetic heart. Transverse aortic constriction (TAC) was performed in non-diabetic (''db''/+) and diabetic (''db''/''db'') mice to induce pressure overload. Magnetic resonance imaging, <sup>31</sup>P magnetic resonance spectroscopy (MRS), <sup>1</sup>H MRS, and <sup>18</sup>F-fluorodeoxyglucose-positron emission tomography (PET) were applied to measure cardiac function, energy status, lipid content, and glucose uptake, respectively. ''In vivo'' measurements were complemented with ''ex vivo'' techniques of high-resolution respirometry, proteomics, and western blotting to elucidate the underlying molecular pathways. In non-diabetic mice, TAC induced progressive cardiac hypertrophy and dysfunction, which correlated with increased protein kinase D-1 (PKD1) phosphorylation and increased glucose uptake. These changes in glucose utilization preceded a reduction in cardiac energy status. At baseline, compared with non-diabetic mice, diabetic mice showed normal cardiac function, higher lipid content and mitochondrial capacity for fatty acid oxidation, and lower PKD1 phosphorylation, glucose uptake, and energetics. Interestingly, TAC affected cardiac function only mildly in diabetic mice, which was accompanied by normalization of phosphorylated PKD1, glucose uptake, and cardiac energy status. The cardiac metabolic adaptations in diabetic mice seem to prevent the heart from failing upon pressure overload, suggesting that restoring the balance between glucose and fatty acid utilization is beneficial for cardiac function.
zation is beneficial for cardiac function.  +
Has editor [[Kandolf G]]  +
Has info [https://www.ncbi.nlm.nih.gov/pubmed/28549111 PMID: 28549111 Open Access]  +
Has publicationkeywords Diabetes  + , Heart failure  + , ''In vivo'' imaging techniques  + , Pressure overload  + , Substrate metabolism  +
Has title Abdurrachim D, Nabben M, Hoerr V, Kuhlmann
Abdurrachim D, Nabben M, Hoerr V, Kuhlmann MT, Bovenkamp P, Ciapaite J, Geraets IME, Coumans W, Luiken JJFP, Glatz JFC, Schäfers M, Nicolay K, Faber C, Hermann S, Prompers JJ (2017) Diabetic db/db mice do not develop heart failure upon pressure overload: a longitudinal ''in vivo'' PET, MRI, and MRS study on cardiac metabolic, structural, and functional adaptations. Cardiovasc Res 113:1148-60.
l adaptations. Cardiovasc Res 113:1148-60.  +
Instrument and method Oxygraph-2k  +
Mammal and model Mouse  +
MiP area Respiration  +
Pathways N  + , S  +
Preparation Isolated mitochondria  +
Tissue and cell Heart  +
Was published by MiPNetLab NL Maastricht Schrauwen P + , NL Groningen Reijngoud RJ + , NL Eindhoven Nicolay K +
Was published in journal Cardiovasc Res +
Was published in year 2017  +
Was written by Abdurrachim D + , Nabben M + , Hoerr V + , Kuhlmann MT + , Bovenkamp P + , Ciapaite J + , Geraets IME + , Coumans W + , Luiken JJFP + , Glatz JFC + , Schaefers M + , Nicolay K + , Faber C + , Hermann S + , Prompers JJ +
Categories Publications
Modification date
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09:22:28, 31 January 2019  +
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