title: TRB3 gene silencing alleviates diabetic cardiomyopathy in a type 2 diabetic rat model.
abstract: OBJECTIVE
  Tribbles 3 (TRB3) is associated with insulin resistance, an important trigger in the development of diabetic cardiomyopathy (DCM). We sought to determine whether TRB3 plays a major role in modulating DCM and the mechanisms involved.
  
  
  METHODS
  The type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin. We evaluated the characteristics of type 2 DCM by serial echocardiography and metabolite tests, Western blot analysis for TRB3 expression, and histopathologic analyses of cardiomyocyte density, lipids accumulation, cardiac inflammation, and fibrosis area. We then used gene silencing to investigate the role of TRB3 in the pathophysiologic features of DCM.
  
  
  RESULTS
  Rats with DCM showed severe insulin resistance, left ventricular dysfunction, aberrant lipids deposition, cardiac inflammation, fibrosis, and TRB3 overexpression. We found that the silencing of TRB3 ameliorated metabolic disturbance and insulin resistance; myocardial hypertrophy, lipids accumulation, inflammation, fibrosis, and elevated collagen I-to-III content ratio in DCM rats were significantly decreased. These anatomic findings were accompanied by significant improvements in cardiac function. Furthermore, with TRB3 gene silencing, the inhibited phosphorylation of Akt was restored and the increased phosphorylation of extracellular signal-regulated kinase 1/2 and Jun NH(2)-terminal kinase in DCM was significantly decreased.
  
  
  CONCLUSIONS
  TRB3 gene silencing may exert a protective effect on DCM by improving selective insulin resistance, implicating its potential role for treatment of human DCM.
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Ji’nan, Shandong Province, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ti
authors.forename: Guo-lu
authors.initials: GL
authors.lastname: Xie
authors.forename: Zhi-hao
authors.initials: ZH
authors.lastname: Wang
authors.forename: Xiao-lei
authors.initials: XL
authors.lastname: Bi
authors.forename: Wen-yuan
authors.initials: WY
authors.lastname: Ding
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.forename: Gui-Hua
authors.initials: GH
authors.lastname: Jiang
authors.forename: Pei-Li
authors.initials: PL
authors.lastname: Bu
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Zhong
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000150:complications*; D058065:Diabetic Cardiomyopathies / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004041:Dietary Fats / Q000009:adverse effects; D004195:Disease Models, Animal; D020868:Gene Silencing; D015316:Genetic Therapy; D006321:Heart / Q000503:physiopathology; D007333:Insulin Resistance; D020935:MAP Kinase Signaling System; D008297:Male; D009206:Myocardium / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D004041:Dietary Fats; D034741:RNA, Small Interfering; C502443:Trib3 protein, rat; D013311:Streptozocin; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt