PMID- 27496100
OWN - NLM
STAT- MEDLINE
DCOM- 20170209
LR  - 20211204
IS  - 1475-2840 (Electronic)
IS  - 1475-2840 (Linking)
VI  - 15
IP  - 1
DP  - 2016 Aug 5
TI  - Transcriptomic alterations in the heart of non-obese type 2 diabetic 
      Goto-Kakizaki rats.
PG  - 110
LID - 10.1186/s12933-016-0424-3 [doi]
LID - 110
AB  - BACKGROUND: 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. 
      METHODS: 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. RESULTS: 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. 
      CONCLUSIONS: 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.
FAU - Sarkozy, Marta
AU  - Sarkozy M
AD  - Department of Biochemistry, Faculty of Medicine, University of Szeged, Dom ter 9, 
      Szeged, 6720, Hungary.
FAU - Szucs, Gergo
AU  - Szucs G
AD  - Department of Biochemistry, Faculty of Medicine, University of Szeged, Dom ter 9, 
      Szeged, 6720, Hungary.
AD  - Department of Physiology, Anatomy and Neuroscience, Faculty of Science and 
      Informatics, University of Szeged, Szeged, Hungary.
FAU - Fekete, Veronika
AU  - Fekete V
AD  - Department of Biochemistry, Faculty of Medicine, University of Szeged, Dom ter 9, 
      Szeged, 6720, Hungary.
FAU - Pipicz, Marton
AU  - Pipicz M
AD  - Department of Biochemistry, Faculty of Medicine, University of Szeged, Dom ter 9, 
      Szeged, 6720, Hungary.
FAU - Eder, Katalin
AU  - Eder K
AD  - Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, 
      Hungary.
FAU - Gaspar, Renata
AU  - Gaspar R
AD  - Department of Biochemistry, Faculty of Medicine, University of Szeged, Dom ter 9, 
      Szeged, 6720, Hungary.
FAU - Soja, Andrea
AU  - Soja A
AD  - Department of Biochemistry, Faculty of Medicine, University of Szeged, Dom ter 9, 
      Szeged, 6720, Hungary.
FAU - Pipis, Judit
AU  - Pipis J
AD  - Pharmahungary Group, Szeged, Hungary.
FAU - Ferdinandy, Peter
AU  - Ferdinandy P
AD  - Pharmahungary Group, Szeged, Hungary.
AD  - Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, 
      Hungary.
FAU - Csonka, Csaba
AU  - Csonka C
AD  - Department of Biochemistry, Faculty of Medicine, University of Szeged, Dom ter 9, 
      Szeged, 6720, Hungary.
FAU - Csont, Tamas
AU  - Csont T
AD  - Department of Biochemistry, Faculty of Medicine, University of Szeged, Dom ter 9, 
      Szeged, 6720, Hungary. csont.tamas@med.u-szeged.hu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160805
PL  - England
TA  - Cardiovasc Diabetol
JT  - Cardiovascular diabetology
JID - 101147637
RN  - 0 (Blood Glucose)
RN  - 0 (Msln protein, rat)
RN  - J27WDC343N (Mesothelin)
SB  - IM
MH  - Animals
MH  - Blood Glucose/*metabolism
MH  - Diabetes Mellitus, Type 2/*metabolism
MH  - Gene Expression/*physiology
MH  - Gene Expression Regulation/*physiology
MH  - Heart/physiopathology
MH  - Male
MH  - Mesothelin
MH  - Metabolic Syndrome/metabolism
MH  - Myocardium/*metabolism
MH  - Rats
MH  - Transcription, Genetic/*physiology
MH  - *Transcriptome
PMC - PMC4975916
OTO - NOTNLM
OT  - DNA microarray
OT  - GO
OT  - Inherited diabetes mellitus
OT  - Insulin resistance
OT  - Myocardium
OT  - Non-obese type 2 diabetes mellitus
OT  - Spontaneous diabetes mellitus
OT  - String
EDAT- 2016/08/09 06:00
MHDA- 2017/02/10 06:00
PMCR- 2016/08/05
CRDT- 2016/08/07 06:00
PHST- 2016/04/11 00:00 [received]
PHST- 2016/07/14 00:00 [accepted]
PHST- 2016/08/07 06:00 [entrez]
PHST- 2016/08/09 06:00 [pubmed]
PHST- 2017/02/10 06:00 [medline]
PHST- 2016/08/05 00:00 [pmc-release]
AID - 10.1186/s12933-016-0424-3 [pii]
AID - 424 [pii]
AID - 10.1186/s12933-016-0424-3 [doi]
PST - epublish
SO  - Cardiovasc Diabetol. 2016 Aug 5;15(1):110. doi: 10.1186/s12933-016-0424-3.