title: Sitagliptin alleviated myocardial remodeling of the left ventricle and improved cardiac diastolic dysfunction in diabetic rats.
abstract: OBJECTIVE
  Sitagliptin, a dipeptidyl peptidase IV (DPP-Ⅳ) inhibitor, has a biological role in improving the serum levels of glucagon-like peptide 1 (GLP-1). Hence, we sought to determine the effect of sitagliptin on myocardial inflammation, collagen metabolism, lipid content and myocardial apoptosis in diabetic rats.
  
  
  METHODS
  The type 2 diabetic rat model was induced by low-dose streptozotocin and a high-fat diet. Characteristics of diabetic rats were evaluated by electrocardiography, echocardiography and blood analysis. Cardiac inflammation, fibrosis, cardiomyocyte density, lipid accumulation, and receptor-interacting protein kinase 3 (RIP3) level, related to apoptosis, were detected by histopathologic analysis, RT-PCR and western blot analysis to evaluate the effects of sitagliptin on myocardial remodeling of the left ventricle.
  
  
  RESULTS
  Diabetic rats showed myocardial hypertrophy or apoptosis, inflammation, lipid accumulation, myocardial fibrosis, elevated collagen content, RIP3 overexpression, and left-ventricular dysfunction. Sitagliptin could reverse the overexpression of RIP3 and alleviate cellular apoptosis in myocardial tissues. It could significantly improve left-ventricular systolic pressure and +dp/dt max, reduce the E/E' ratio, left ventricular end diastolic pressure, -dp/dt max and Tau in diabetic rats.
  
  
  CONCLUSIONS
  Sitagliptin might have a myocardial protective effect by inhibiting apoptosis, inflammation, lipid accumulation and myocardial fibrosis in diabetic rats, for a potential role in improving left-ventricular function in diabetes.
authors.affiliation: Department of Cardiology, The Qilu Hospital of Shandong University, Jinan, Shandong, 250033, PR China; Department of Cardiology, The Second Hospital of Shandong University, Jinan, Shandong, 250033, PR China. Electronic address: lyssyl188@sina.com.
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The Qilu Hospital of Shandong University, Jinan, Shandong, 250033, PR China. Electronic address: huangzhiwei88@tom.com.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Huang
authors.affiliation: Department of Cardiology, The Qilu Hospital of Shandong University, Jinan, Shandong, 250033, PR China. Electronic address: wanglin2004@yahoo.com.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The Qilu Hospital of Shandong University, Jinan, Shandong, 250033, PR China. Electronic address: liuxx@tom.com.
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The Second Hospital of Shandong University, Jinan, Shandong, 250033, PR China. Electronic address: xinzang2012@126.com.
authors.forename: Yong-Mei
authors.initials: YM
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The Qilu Hospital of Shandong University, Jinan, Shandong, 250033, PR China. Electronic address: daixh@vip.sina.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The Qilu Hospital of Shandong University, Jinan, Shandong, 250033, PR China. Electronic address: daixh@vip.sina.com.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D003971:Diastole; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000473:pathology; D017208:Rats, Wistar; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D000068900:Sitagliptin Phosphate / Q000494:pharmacology* / Q000627:therapeutic use*; D013311:Streptozocin; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D013311:Streptozocin; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C582791:Ripk3 protein, rat; D000068900:Sitagliptin Phosphate
keywords: Cardiac function; Diabetes mellitus; Myocardial remodeling; Sitagliptin