{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:41:06Z","timestamp":1782877266343,"version":"3.54.5"},"reference-count":41,"publisher":"American Physiological Society","issue":"4","funder":[{"name":"Deutsche Gesellschaft f\u00fcr Kardiologie (German Cardiac Society)"},{"name":"Medical Faculty of the University of Heidelberg"},{"DOI":"10.13039\/501100003549","name":"Orsz\u00e1gos Tudom\u00e1nyos Kutat\u00e1si Alapprogramok (Hungarian Scientific Research Fund)","doi-asserted-by":"publisher","award":["OTKA PD100245"],"award-info":[{"award-number":["OTKA PD100245"]}],"id":[{"id":"10.13039\/501100003549","id-type":"DOI","asserted-by":"publisher"}]},{"name":"J\u00e1nos Bolyai Research Scholarship of the Hungarian Academy of Sciences"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2016,10,1]]},"abstract":"<jats:p> 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 \u00b1 0.04 vs. 0.05 \u00b1 0.01 mmHg\/\u03bcl, P &lt; 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-1\u03b2, and tumor necrosis factor (TNF)-\u03b1 mRNA-level]. Of the altered genes, which were evaluated by Western blot, only TNF-\u03b1 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-\u03b1 at both the mRNA and protein levels. Further assessments are required to reveal if TNF-\u03b1 plays a role in the early stage of diabetic cardiomyopathy development. <\/jats:p>","DOI":"10.1152\/ajpheart.00956.2015","type":"journal-article","created":{"date-parts":[[2016,8,12]],"date-time":"2016-08-12T22:19:13Z","timestamp":1471040353000},"page":"H958-H971","source":"Crossref","is-referenced-by-count":23,"title":["Left ventricular pressure-volume measurements and myocardial gene expression profile in type 2 diabetic Goto-Kakizaki rats"],"prefix":"10.1152","volume":"311","author":[{"given":"Sevil","family":"Korkmaz-Ic\u00f6z","sequence":"first","affiliation":[{"name":"Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Lehner","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, University of Heidelberg, Heidelberg, 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