Left ventricular pressure-volume measurements and myocardial gene expression profile in type 2 diabetic Goto-Kakizaki rats

• Verfasst von: Korkmaz-İçöz, Sevil [VerfasserIn]
• Verfasst von: Lehner, Alice [VerfasserIn]
• Verfasst von: Li, Shiliang [VerfasserIn]
• Verfasst von: Brune, Maik [VerfasserIn]
• Verfasst von: Ruppert, Mihály [VerfasserIn]
• Verfasst von: Brlecic, Paige [VerfasserIn]
• Verfasst von: Zorn, Markus [VerfasserIn]
• Verfasst von: Karck, Matthias [VerfasserIn]
• Verfasst von: Szabó, Gábor [VerfasserIn]
• Titel: Left ventricular pressure-volume measurements and myocardial gene expression profile in type 2 diabetic Goto-Kakizaki rats
• Verf.angabe: 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
• E-Jahr: 2016
• Jahr: 29 July 2016
• Umfang: 14 S.
• Fussnoten: Gesehen am 19.05.2020
• Titel Quelle: Enthalten in: American journal of physiology / Heart and circulatory physiology
• Ort Quelle: Bethesda, Md. : American Physiological Society, 1977
• Jahr Quelle: 2016
• Band/Heft Quelle: 311(2016,4) Artikel-Nummer H958-H971, 14 Seiten
• ISSN Quelle: 1522-1539
• DOI: doi:10.1152/ajpheart.00956.2015
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1698513232

Abstract

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.