title: Transcriptomic alterations in the heart of non-obese type 2 diabetic Goto-Kakizaki rats.
abstract: There is a spectacular rise in the global prevalence of type 2 diabetes mellitus (T2DM) due to the worldwide obesity epidemic. However, a significant proportion of T2DM patients are non-obese and they also have an increased risk of cardiovascular diseases. As the Goto-Kakizaki (GK) rat is a well-known model of non-obese T2DM, the goal of this study was to investigate the effect of non-obese T2DM on cardiac alterations of the transcriptome in GK rats.
  
  
  
  Fasting blood glucose, serum insulin and cholesterol levels were measured at 7, 11, and 15 weeks of age in male GK and control rats. Oral glucose tolerance test and pancreatic insulin level measurements were performed at 11 weeks of age. At week 15, total RNA was isolated from the myocardium and assayed by rat oligonucleotide microarray for 41,012 genes, and then expression of selected genes was confirmed by qRT-PCR. Gene ontology and protein-protein network analyses were performed to demonstrate potentially characteristic gene alterations and key genes in non-obese T2DM.
  
  
  
  Fasting blood glucose, serum insulin and cholesterol levels were significantly increased, glucose tolerance and insulin sensitivity were significantly impaired in GK rats as compared to controls. In hearts of GK rats, 204 genes showed significant up-regulation and 303 genes showed down-regulation as compared to controls according to microarray analysis. Genes with significantly altered expression in the heart due to non-obese T2DM includes functional clusters of metabolism (e.g. Cyp2e1, Akr1b10), signal transduction (e.g. Dpp4, Stat3), receptors and ion channels (e.g. Sln, Chrng), membrane and structural proteins (e.g. Tnni1, Mylk2, Col8a1, Adam33), cell growth and differentiation (e.g. Gpc3, Jund), immune response (e.g. C3, C4a), and others (e.g. Lrp8, Msln, Klkc1, Epn3). Gene ontology analysis revealed several significantly enriched functional inter-relationships between genes influenced by non-obese T2DM. Protein-protein interaction analysis demonstrated that Stat is a potential key gene influenced by non-obese T2DM.
  
  
  
  Non-obese T2DM alters cardiac gene expression profile. The altered genes may be involved in the development of cardiac pathologies and could be potential therapeutic targets in non-obese T2DM.
authors: Department of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér 9, Szeged, 6720, Hungary.
authors: Márta
authors: M
authors: Sárközy
authors: Department of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér 9, Szeged, 6720, Hungary.|Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary.
authors: Gergő
authors: G
authors: Szűcs
authors: Department of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér 9, Szeged, 6720, Hungary.
authors: Veronika
authors: V
authors: Fekete
authors: Department of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér 9, Szeged, 6720, Hungary.
authors: Márton
authors: M
authors: Pipicz
authors: Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
authors: Katalin
authors: K
authors: Éder
authors: Department of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér 9, Szeged, 6720, Hungary.
authors: Renáta
authors: R
authors: Gáspár
authors: Department of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér 9, Szeged, 6720, Hungary.
authors: Andrea
authors: A
authors: Sója
authors: Pharmahungary Group, Szeged, Hungary.
authors: Judit
authors: J
authors: Pipis
authors: Pharmahungary Group, Szeged, Hungary.|Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
authors: Péter
authors: P
authors: Ferdinandy
authors: Department of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér 9, Szeged, 6720, Hungary.
authors: Csaba
authors: C
authors: Csonka
authors: Department of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér 9, Szeged, 6720, Hungary. csont.tamas@med.u-szeged.hu.
authors: Tamás
authors: T
authors: Csont
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006321:Heart / Q000503:physiopathology; D008297:Male; D000090204:Mesothelin; D024821:Metabolic Syndrome / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D014158:Transcription, Genetic / Q000502:physiology*; D059467:Transcriptome
chemical_list: D001786:Blood Glucose; C000715529:Msln protein, rat; D000090204:Mesothelin
keywords: DNA microarray; GO; Inherited diabetes mellitus; Insulin resistance; Myocardium; Non-obese type 2 diabetes mellitus; Spontaneous diabetes mellitus; String