Hung, C.-L.C.-L.HungSZU-HUA PANHan, C.-L.C.-L.HanChang, C.-W.C.-W.ChangHsu, Y.-L.Y.-L.HsuSu, C.-H.C.-H.SuShih, S.-C.S.-C.ShihLai, Y.-J.Y.-J.LaiChiau, J.-S.C.J.-S.C.ChiauYeh, H.-I.H.-I.YehLiu, C.-Y.C.-Y.LiuLee, H.-C.H.-C.LeeLam, C.S.P.C.S.P.Lam2019-08-272019-08-2720171535-38931535-3907http://www.scopus.com/inward/record.url?eid=2-s2.0-85044110620&partnerID=MN8TOARShttps://scholars.lib.ntu.edu.tw/handle/123456789/416698© 2017 American Chemical Society. Diabetic cardiomyopathy is a well-recognized complication of diabetes, but its pathophysiology is unclear. We aimed to investigate the mechanisms underlying cardiac dysfunction in an elderly type 2 diabetic (T2DM) mouse model, using membrane proteomic analyses. Elderly mice were fed a high fat diet for 12 weeks to induce T2DM, and myocardial structure and function were assessed by echocardiography. Cardiomyocytes were isolated by Langendorff perfusion and subjected to iTRAQ-based quantitative membrane proteomic profiling, immunoblotting, and real-time quantitative reverse-transcriptase polymerase chain reaction. Compared to controls, elderly T2DM mice showed worse systolic function, more myocardial fibrosis and up-regulation of several heart failure markers (all p < 0.05). Cardiomyocyte membrane proteomic profiling revealed that 417 proteins had differential expressions related to perturbations in several biological processes in T2DM mice compared with the control. The most up-regulated proteins were involved in oxidative phosphorylation, whereas many down-regulated proteins were involved in cytoskeletal regulation. Differential protein expression correlated with myocardial systolic velocity by tissue Doppler. In addition, cardiomyocyte immunofluorescence staining showed greater disorganization of thick/parallel F-actin stress fibers and marked reduction in F-to-G-actin ratio in T2DM vs control (p < 0.05), which paralleled worsened myocardial systolic velocity. We concluded that cardiac contractile dysfunction in elderly T2DM mice was associated with impaired energetics and cytoskeletal disorganization.enCytoskeletal proteins | Diabetic cardiomyopathy | F-actin | G-actin | High fat diet | ITRAQ membrane proteomic profiling | Oxidative phosphorylation | Type 2 diabetes (T2DM)Cytoskeletal proteins; Diabetic cardiomyopathy; F-actin; G-actin; High fat diet; ITRAQ membrane proteomic profiling; Oxidative phosphorylation; Type 2 diabetes (T2DM)[SDGs]SDG3biological marker; collagen type 1; F actin; G actin; glucagon like peptide 1; glucagon like peptide 1 receptor; actin; membrane protein; animal cell; animal experiment; animal model; animal tissue; Article; cardiac muscle cell; controlled study; cytoskeleton; diabetic cardiomyopathy; echocardiography; energy transfer; heart failure; heart muscle contractility; heart muscle fibrosis; immunoblotting; immunofluorescence; isolated heart; lipid diet; liquid chromatography-mass spectrometry; male; mouse; non insulin dependent diabetes mellitus; nonhuman; oxidative phosphorylation; priority journal; protein expression; proteomics; quantitative analysis; real time polymerase chain reaction; reverse transcription polymerase chain reaction; stress fiber; systole; tissue Doppler imaging; upregulation; animal; cardiac muscle; complication; cytoskeleton; disease model; energy metabolism; fibrosis; gene expression regulation; genetics; human; metabolism; non insulin dependent diabetes mellitus; pathology; Actins; Animals; Cytoskeleton; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Diet, High-Fat; Disease Models, Animal; Energy Metabolism; Fibrosis; Gene Expression Regulation; Humans; Membrane Proteins; Mice; Myocardium; Myocytes, Cardiac; Proteomicsjournal article10.1021/acs.jproteome.7b0014860947662288231692-s2.0-85044110620WOS:000412789400003http://www.scopus.com/inward/record.url?eid=2-s2.0-85044110620&partnerID=MN8TOARS60947662