Left ventricular pressure-volume measurements and myocardial gene expression profile in type 2 diabetic Goto-Kakizaki rats
The Goto-Kakizaki (GK) rat, a non-obese model of type 2 diabetes mellitus (T2DM), was generated by the selective inbreeding of glucose-intolerant Wistar rats. This is a convenient model for studying diabetes-induced cardiomyopathy independently from the effects of the metabolic syndrome. We investig...
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| Main Authors: | , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
29 July 2016
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| In: |
American journal of physiology. Heart and circulatory physiology
Year: 2016, Volume: 311, Issue: 4, Pages: 1-14 |
| ISSN: | 1522-1539 |
| DOI: | 10.1152/ajpheart.00956.2015 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1152/ajpheart.00956.2015 Verlag, lizenzpflichtig, Volltext: https://journals.physiology.org/doi/full/10.1152/ajpheart.00956.2015 
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| Author Notes: | Sevil Korkmaz-Icöz, Alice Lehner, Shiliang Li, Adrian Vater, Tamás Radovits, Maik Brune, Mihály Ruppert, Xiaoxin Sun, Paige Brlecic, Markus Zorn, Matthias Karck, and Gábor Szabó |
| Summary: | The Goto-Kakizaki (GK) rat, a non-obese model of type 2 diabetes mellitus (T2DM), was generated by the selective inbreeding of glucose-intolerant Wistar rats. This is a convenient model for studying diabetes-induced cardiomyopathy independently from the effects of the metabolic syndrome. We investigated the myocardial functional and structural changes and underlying molecular pathomechanisms of short-term and mild T2DM. The presence of DM was confirmed by an impaired oral glucose tolerance in the GK rats compared with the age-matched nondiabetic Wistar rats. Data from cardiac catheterization showed that in GK rats, although the systolic indexes were not altered, the diastolic stiffness was increased compared with nondiabetics (end-diastolic-pressure-volume-relationship: 0.12 ± 0.04 vs. 0.05 ± 0.01 mmHg/μl, P < 0.05). Additionally, DM was associated with left-ventricular hypertrophy and histological evidence of increased myocardial fibrosis. The plasma pro-B-type natriuretic peptide, the cardiac troponin-T, glucose, and the urinary glucose concentrations were significantly higher in GK rats. Among the 125 genes surveyed using PCR arrays, DM significantly altered the expression of five genes [upregulation of natriuretic peptide precursor-A and connective tissue growth factor, downregulation of c-reactive protein, interleukin-1β, and tumor necrosis factor (TNF)-α mRNA-level]. Of the altered genes, which were evaluated by Western blot, only TNF-α protein expression was significantly decreased. The ECG recordings revealed no significant differences. In conclusion, while systolic dysfunction, myocardial inflammation, and abnormal electrical conduction remain absent, short-term and mild T2DM induce the alteration of cardiac TNF-α at both the mRNA and protein levels. Further assessments are required to reveal if TNF-α plays a role in the early stage of diabetic cardiomyopathy development. |
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| Item Description: | Gesehen am 19.05.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1522-1539 |
| DOI: | 10.1152/ajpheart.00956.2015 |