scholarly journals Elucidation of The Effects and Underlying Mechanism of Aerobic Interval Training Combined With Liraglutide On Diabetic Cardiomyopathy

Author(s):  
Huan Cai ◽  
Linling Zhou ◽  
Jingqin Liu ◽  
Zelin Li ◽  
Shuchun Chen

Abstract objective: This study intended to explore the hypoglycemic and cardioprotective effects of 8-week aerobic interval training combined with liraglutide and elucidate the underlying mechanisms.Method: Male Wistar rats were randomly divided into 5 groups - normal control (CON), diabetic cardiomyopathy (DCM), high-dose liraglutide (DH), low-dose liraglutide DL , and aerobic interval training combined with liraglutide (DLE). The cardiac function of rats ,the FBG the levels of fasting insulin (FIN), HbA1c, the total collagen content , AGEs, the mRNA expression of myocardial remodeling genes BNP, GSK3β, α-MHC, and β-MHC ,the expression of GLP-1 and GLP-1R proteins, Insulin resistance (HOMA-IR) and beta-cell function (HOMA-β) was analyze. Results: During the intervention, the FBG in each intervention group significantly decreased compared to the DCM group. After 8 weeks,the DH, DL, and DLE groups showed improved blood glucose-related indices and cleared the accumulated AGEs in the DCM groups. The heart function in the DLE groups was significantly improved than that in the DH and DL groups. The relative expression of BNP mRNA in the DH, DL, and DLE groups significantly reduced compared to the CON and the DCM group .Compared to the DCM group,the relative expression of α-MHC mRNA increased significantly and β-MHC mRNA decreased notably in the myocardium of the DH, DL, and the DLE group.The expression of GLP-1 in the myocardial tissue of rats in the DH group was higher than that in the DL and DLE groups. GLP-1R expression in the myocardial tissue in the DLE group was higher than that in the DH , DL and the DCM groups .Conclusion: Liraglutide combined with AIT intervention significantly reduced FBG and the fluctuations in FBG, alleviated myocardial fibrosis, improved cardiac function in DCM rats, supporting the efficacy of the combined pharmaceutical and physical intervention, and reduced the cost of treatment.

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Dongtak Jeong ◽  
Changwon Kho ◽  
Ahyoung Lee ◽  
Woo Jin Park ◽  
Roger Hajjar

CCN family members are matricellular proteins with diverse roles in cell function. Recently, we showed that the differential expression of CCN2 and CCN5 during cardiac remodeling suggests that these two members of the CCN family play opposing roles during the development of cardiac hypertrophy and fibrosis. Since it is reported that an underlying morphological correlate of diastolic dysfunction is cardiac fibrosis, which leads to increased stiffness of the heart, we aimed to evaluate the role of CCN5 on cardiac fibrosis and function by the gene delivery using the cardiotropic AAV9 vector. We generated pressure-overload heart failure models in mouse by TAC operation. After 8-10 weeks of TAC on mice, HF was confirmed by Echocardiography. In those HF mice, AAV9-GFP (control) and AAV9-CCN5 were addressed by IV. Two more months later, cardiac function was evaluated by echocardiography and invasive hemodynamics. Protein and RNA expression levels of CCN5, several types of collagen and conventional TGF-beta signaling related genes were evaluated by western blot and quantitative real time PCR analysis. First, we were able to achieve about 4-5 fold increase of CCN5 expression by AAV9-CCN5 injection without any change in heart function. Second, CCN5 expression level in blood was not significantly altered after AAV9-CCN5 gene transfer because it may be the result of the cardiac tropism of the vector used. The HF model by TAC surgery was confirmed with echocardiography (FS (%)). Overall average FS (%) in HF was 41.87+/− 5.27 (n=16) and in non-surgery control mice was 58.39 +/− 2.06(n=4). After AAV9 injection, cardiac function of CCN5 injected mice was sustained but AAV9-GFP injected mice showed severe cardiac dysfunction and dilation (AAV-GFP (24.29+/− 9.11) vs AAV-CCN5 (42.66 +/− 4.73)). Third, western blot analysis showed that the downstream effectors, namely TGF-beta signaling pathways were significantly down-regulated in CCN5 injected mice. In addition, fibrotic area of the heart was tremendously reduced. Finally, CCN5 expression is significantly decreased in human heart failure patients compared to those in nonfailing donors. Taken together our data would indicate that CCN5 may be a promising therapeutic target to reduce cardiac fibrosis.


2010 ◽  
Vol 109 (6) ◽  
pp. 1749-1755 ◽  
Author(s):  
Madelene Ericsson ◽  
Cecilie Sjåland ◽  
Kristin B. Andersson ◽  
Ivar Sjaastad ◽  
Geir Christensen ◽  
...  

In the heart, function of the sarco(endo)plasmic Ca2+-ATPase (SERCA2) is closely linked to contractility, cardiac function, and aerobic fitness. SERCA2 function can be increased by high-intensity interval training, whereas reduced SERCA2 abundance is associated with impaired cardiac function. The working hypothesis was, therefore, that exercise training before cardiomyocyte-specific disruption of the Serca2 gene would delay the onset of cardiac dysfunction in mice. Before Serca2 gene disruption by tamoxifen, untreated SERCA2 knockout mice ( Serca2flox/flox Tg-αMHC-MerCreMer; S2KO), and SERCA2 FF control mice ( Serca2flox/flox, S2FF) were exercise trained by high-intensity interval treadmill running for 6 wk. Both genotypes responded to training, with comparable increases in maximal oxygen uptake (V̇o2max; 17%), left ventricle weight (15%), and maximal running speed (40%). After exercise training, cardiac-specific Serca2 gene disruption was induced in both exercise trained and sedentary S2KO mice. In trained S2KO, cardiac function decreased less rapidly than in sedentary S2KO. V̇o2max remained higher in trained S2KO the first 15 days after gene disruption. Six weeks after Serca2 disruption, cardiac output was higher in trained compared with sedentary S2KO mice. An exercise-training program attenuates the decline in cardiac performance induced by acute cardiac Serca2 gene disruption, indicating that mechanisms other than SERCA2 contribute to the favorable effect of exercise training.


2021 ◽  
Vol 67 (3) ◽  
pp. 201-203
Author(s):  
Jianjun Li ◽  
Xiaoxiao Li ◽  
Xiaoming Qiao

Type 1 diabetes mellitus, also called insulin-dependent diabetes is associated with elevated blood glucose concentration arising from the inability of the pancreas to produce insulin. Diabetic cardiomyopathy is a major cause of death in diabetic patients. CircRNAs have been reported to participate in various human diseases, including diabetic cardiomyopathy. In this study, the regulation network of circRNA in type 1 diabetes mellitus was investigated. Streptozotocin treatment was implemented to induce type 1 diabetes mellitus in the mouse model, and echocardiography was implemented to detect the heart function of the type 1 diabetes mellitus mouse. Also, the qRT-PCR assay was used to identify the circRNA expression in type 1 diabetes mellitus mouse myocardial tissue. Findings showed that heart function of type 1 diabetes mellitus mouse was significantly damaged than control group mouse and cardiac hypertrophy in type 1 diabetes mellitus mouse, circRNAs were aberrantly regulated in type 1 diabetes mellitus mouse myocardial tissue. The following circRNAs were mmu_circ_0001560, mmu_circ_0001800, mmu_circ_0001801, mmu_circ_0002281 and mmu_circ_0000614 were expressed low in type 1 diabetes mellitus mouse myocardial tissue. In conclusion, type 1 diabetes mellitus caused alterations in the regulation network of circRNAs.


2012 ◽  
Vol 46 (3) ◽  
pp. 163-171 ◽  
Author(s):  
Harald Edvard Molmen ◽  
Ulrik Wisloff ◽  
Inger Lise Aamot ◽  
Asbjorn Stoylen ◽  
Charlotte Bjork Ingul

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Ya-Ru Bao ◽  
Wen-Yi Jiang ◽  
Jia-Yu Yu ◽  
Jing-Wei Chen ◽  
Guo-Xing Zhang

Huangqi Jianzhong Tang (HQJZT) is a traditional Chinese herbal formula consisting of seven different herbs: Radix Astragali, Radix Paeoniae Alba, Ramulus Cinnamomi, Fructus Jujubae, Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle, Rhizoma Zingiberis Recens, and Saccharum Granorum. The present study aims to evaluate the possible effects of HQJZT on cardiac function in acute myocardial infarction (AMI) and related mechanism. AMI model was established by ligation of the left anterior descending coronary artery followed by one-week HQJZT treatment. Survival rate was calculated. Rat heart function was assessed by heart performance analysis system. 5-Triphenyltetrazolium chloride (TTC) staining was used to observe myocardial infarct size. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining and western blot were applied to evaluate tissue apoptotic level. Treatment with high dose of HQJZT improved cardiac function, reduced infarct size, number of apoptotic cells and expression of apoptotic proteins, Bax (a proapoptotic protein), and increased expression of antiapoptotic protein, Bcl2. However, enalapril (an angiotensin-converting enzyme inhibitor) treatment did not show marked improvement of these parameters. Our present data suggest that HQJZT has potential therapeutic effects to improve cardiac function by regulation of apoptotic signaling pathway.


1989 ◽  
Vol 67 (6) ◽  
pp. 629-636 ◽  
Author(s):  
Brian Rodrigues ◽  
Gail M. McGrath ◽  
John H. McNeill

Cardiac abnormalities observed in animals with drug-induced diabetes may be due to the direct cardiotoxic effect of the drugs or factors not related to the diabetic state. The purpose of this investigation was to examine cardiac sarcoplasmic reticular (SR) calcium transport and heart function in the BB rat, a strain in which diabetes occurs spontaneously and clearly resembles insulin-dependent diabetes in humans. Complete insulin withdrawal for 2 or 4 days from BB diabetic rats leads to a spectrum of metabolic derangements including a loss of body weight, hyperglycemia, and elevated triglyceride levels confirming the insulin dependence of this model. The present study involved treating BB diabetic rats with a low (hyperglycemic) and high (normoglycemic) insulin dose for 12 weeks after the detection of glycosuria. The hearts from these animals were then isolated, and SR Ca2+ transport and heart function (using isolated perfused working hearts) were examined and compared with BB nondiabetic littermates or Wistar controls. Strain-related differences were found in ATP-dependent SR Ca2+ transport between the Wistar and BB rats. There were, however, no significant diabetes-related differences in SR Ca2+ transport between the low dose insulin treated diabetic group (LD) and the high dose insulin treated diabetic group (HD) or the nondiabetic littermates. Plasma lipid concentrations of the LD and HD BB rats and nondiabetic littermates were also generally higher than those of control Wistar rats indicating strain-related but not diabetes-related differences. In addition, there were no differences in cardiac function between the LD and BB nondiabetic littermates or Wistar controls. These studies suggest that since persistent hyperglycemia in the LD BB rat produced no significant physiological abnormalities in the heart, other factors must be contributing to the depression of heart function noted during diabetes.Key words: diabetes, BB rat, sarcoplasmic reticular calcium transport, heart function.


2013 ◽  
Vol 118 (4) ◽  
pp. 796-808 ◽  
Author(s):  
Pornswan Ngamprasertwong ◽  
Erik C. Michelfelder ◽  
Shahriar Arbabi ◽  
Yun Suk Choi ◽  
Christopher Statile ◽  
...  

Abstract Background: Use of high-dose inhalational anesthesia during open fetal surgery may induce maternal–fetal hemodynamic instability and fetal myocardial depression. The authors’ preliminary human retrospective study demonstrated less fetal bradycardia and left ventricular systolic dysfunction with lower dose desflurane supplemented with propofol and remifentanil IV anesthesia (SIVA). In this animal study, the authors compare maternal–fetal effects of high-dose desflurane anesthesia (HD-DES) and SIVA. Methods: Of 26 instrumented midgestational ewes, data from 11 animals exposed to both SIVA and HD-DES in random sequences and six animals exposed to HD-DES while maternal normotension was maintained were analyzed. Maternal electroencephalography was used to guide comparable depths of anesthesia in both techniques. Hemodynamic parameters, blood gas, and fetal cardiac function from echocardiography were recorded. Results: Compared with SIVA, HD-DES resulted in significant maternal hypotension (mean arterial pressure difference, 19.53 mmHg; 95% CI, 17.6–21.4; P < 0.0001), fetal acidosis (pH 7.11 vs. 7.24 at 150 min, P < 0.001), and decreased uterine blood flow. In the HD-DES group with maternal normotension, uterine blood flow still declined and fetal acidosis persisted, with no statistically significant difference from the group exposed to HD-DES that had maternal hypotension. There was no statistically significant difference in fetal cardiac function. Conclusion: In sheep, SIVA affects maternal hemodynamics less and provides better fetal acid/base status than high-dose desflurane. Fetal echocardiography did not reflect myocardial dysfunction in this model.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tarun Pant ◽  
Anuradha Dhanasekaran ◽  
Ming Zhao ◽  
Edward B. Thorp ◽  
Joseph M. Forbess ◽  
...  

AbstractDiabetic cardiomyopathy (DCM) lacks diagnostic biomarkers. Circulating long non-coding RNAs (lncRNAs) can serve as valuable diagnostic biomarkers in cardiovascular disease. To seek potential lncRNAs as a diagnostic biomarker for DCM, we investigated the genome-wide expression profiling of circulating lncRNAs and mRNAs in type 2 diabetic db/db mice with and without DCM and performed bioinformatic analyses of the deregulated lncRNA-mRNA co-expression network. Db/db mice had obesity and hyperglycemia with normal cardiac function at 6 weeks of age (diabetes without DCM) but with an impaired cardiac function at 20 weeks of age (DCM) on an isolated Langendorff apparatus. Compared with the age-matched controls, 152 circulating lncRNAs, 127 mRNAs and 3355 lncRNAs, 2580 mRNAs were deregulated in db/db mice without and with DCM, respectively. The lncRNA-mRNA co-expression network analysis showed that five deregulated lncRNAs, XLOC015617, AK035192, Gm10435, TCR-α chain, and MouselincRNA0135, have the maximum connections with differentially expressed mRNAs. Bioinformatic analysis revealed that these five lncRNAs were highly associated with the development and motion of myofilaments, regulation of inflammatory and immune responses, and apoptosis. This finding was validated by the ultrastructural examination of myocardial samples from the db/db mice with DCM using electron microscopy and changes in the expression of myocardial tumor necrosis factor-α and phosphorylated p38 mitogen-activated protein kinase in db/db mice with DCM. These results indicate that XLOC015617, AK035192, Gm10435, TCR-α chain, and MouselincRNA0135 are crucial circulating lncRNAs in the pathogenesis of DCM. These five circulating lncRNAs may have high potential as a diagnostic biomarker for DCM.


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