title: Left ventricular deformation associated with cardiomyocyte Ca(2+) transients delay in early stage of low-dose of STZ and high-fat diet induced type 2 diabetic rats.
abstract: BACKGROUND
  In the early stage of diabetes, the cardiac ejection fraction is preserved, despite the existence of the subclinical cardiac dysfunction to some extent. However, the detailed phenotype of this dysfunction and the underlying mechanism remain unclear. To improve our understanding of this issue, we used low-dose STZ and high-fat diet to induce type 2 diabetic models in rats. The effects and the mechanism associated with the early stages of the disease were analyzed.
  
  
  METHODS
  The type 2 diabetic mellitus (T2DM) in SD rats were induced through 30 mg/kg STZ and high-fat diet. Two-dimensional spackle-tracking echocardiography (STE) and the dobutamine test were performed to examine the cardiac function. Calcium transients of left ventricular myocytes were detected and the related intracellular signalling factors were analyzed by western blotting.
  
  
  RESULTS
  After 6-weeks, T2DM rats in left ventricular (LV) diastole showed decreased global and segment strain(S) levels (P < 0.05), both in the radial and circumferential directions. Strain rate (Sr) abatement occurred in three segments in the radial and circumferential directions (P < 0.05), and the radial global Sr also decreased (P < 0.05). In the systolic LV, radial Sr was reduced, except the segment of the anterior septum, and the Sr of the lateral wall and post septum decreased in the circumferential direction (P < 0.05). Conventional M-mode echocardiography failed to detect significant alterations of cardiac performance between the two groups even after 12 weeks, and the decreased ejection fraction (EF%), fractional shortening (FS%) and end-systolic diameters (ESD) could be detected only under stress conditions induced by dobutamine (P < 0.05). In terms of calcium transients in cardiac myocytes, the Tpeak in model rats at 6 weeks was not affected, while the Tdecay1/2 was higher than that of the controls (P < 0.05), and both showed a dose-dependent delay after isoproterenol treatment (P < 0.05). Western blot analysis showed that in 6-week T2DM rats, myocardial p-PLB expression was elevated, whereas p-CaMKII, p-AMPK and Sirt1 were significantly down-regulated (P < 0.05).
  
  
  CONCLUSIONS
  A rat model of T2DM was established by low dose STZ and a high-fat diet. LV deformation was observed in the early stages of T2DM in association with the delay of Ca(2+) transients in cardiomyocytes due to the decreased phosphorylation of CaMKII. Myocardial metabolism remodeling might contribute to the early LV function and calcium transportation abnormalities.
authors.affiliation: Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China.
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Liu
authors.affiliation: Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China.|Department of Cardiology of the First Affiliated Hospital, Jinan University, Guangzhou, 510630, P.R. China.
authors.forename: Fu-Cheng
authors.initials: FC
authors.lastname: Liu
authors.affiliation: Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Deng
authors.affiliation: Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China.
authors.forename: Meng-Zhen
authors.initials: MZ
authors.lastname: Zhang
authors.affiliation: Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China.
authors.forename: Ding-Zhang
authors.initials: DZ
authors.lastname: Xiao
authors.affiliation: Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China.
authors.forename: Qiu-Xiong
authors.initials: QX
authors.lastname: Lin
authors.affiliation: Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China.
authors.forename: Shi-Ting
authors.initials: ST
authors.lastname: Cai
authors.affiliation: Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China.
authors.forename: Su-Juan
authors.initials: SJ
authors.lastname: Kuang
authors.affiliation: Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China.
authors.forename: Shao-Xian
authors.initials: SX
authors.lastname: Chen
authors.affiliation: Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China.
authors.forename: Jie-Ning
authors.initials: JN
authors.lastname: Zhu
authors.affiliation: Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Rao
authors.affiliation: Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China.
authors.forename: Yong-Heng
authors.initials: YH
authors.lastname: Fu
authors.affiliation: Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China. yuxycn@aliyun.com.|Institute of Molecular and Clinical Pharmacology, Guangzhou Medical University, Guangzhou, 511436, P.R. China. yuxycn@aliyun.com.
authors.forename: Xi-Yong
authors.initials: XY
authors.lastname: Yu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D058065:Diabetic Cardiomyopathies / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004452:Echocardiography; D025401:Echocardiography, Stress; D004591:Electrophoresis, Polyacrylamide Gel; D006352:Heart Ventricles / Q000166:cytology / Q000000981:diagnostic imaging / Q000378:metabolism*; D015151:Immunoblotting; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism; D000099211:Phospholamban
chemical_list: D055372:AMP-Activated Protein Kinases; D002118:Calcium; D002135:Calcium-Binding Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D010750:Phosphoproteins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D056564:Sirtuin 1; D000099211:Phospholamban; C488368:Sirt1 protein, rat