Exercise as A Potential Therapeutic Target for Diabetic Cardiomyopathy: Insight into the Underlying Mechanisms
Abstract
:1. Introduction
2. Clinical Aspects of DCM
2.1. Definition and Characteristics of DCM
2.2. Treatment Strategies for DCM
2.3. Clinical Significance of Exercise for the Treatment of DCM
3. Potential Mechanisms of Protective Effects of Exercise Against DCM
3.1. Cardiac Cell Metabolism
3.2. Calcium Regulation in Cardiac Cells
3.3. Mitochondrial Function of Cardiac Cells
3.4. Oxidative Stress in Cardiomyocytes
3.5. Myocardial Fibrosis
3.6. Apoptosis of Cardiomyocytes
3.7. Microvascular Function of Cardiomyocytes
4. Prospective New Biomarkers in DCM
5. Clinical Perspective on the Future Use of Exercise in DCM Prevention
Exercise Is an Early Diagnostic Tool for Prevention and Better Treatment of DCM
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Study Type (Design) | Subjects | Exercise Intervention | Effects | Ref | |||
---|---|---|---|---|---|---|---|
Type | Frequency | Time (min) | Duration | ||||
Human (non-RCT) | Patients with T2DM | Home-based exercise training (Rowing ergo meter) | 3–4 days/wk | 30 m every other day for a total of 28 sessions | 8 wks | ↑Insulin sensitivity ↑Forearm endothelial function ↓Plasma adhesion molecules (ICAM-1 & VCAM-1) | [43] |
Human (RCT) | Patients with T2DM | Aerobic & Resistance Exercise | 3–5 days/wk | 75 min/session | 12 wks | ↑Anti-atherosclerotic effects ↓Cardiovascular events ↑Flow-mediated endothelium-dependent vasodilation | [45] |
Human (non-RCT) | Patients with T2DM | Aerobic Exercise | 4 days/wk | 4–7 h/day | 24 wks | ↓Hepatic triglyceride ↓Paracardial fat volume | [46] |
Human (RCT) | Patients with T2DM | High intensity interval training | NA | NA | 12 wks | ↑Left ventricular mass (g) ↑Early diastolic filling rate change (ml/s) ↑Peak torsion change ↓Body weight (kg) ↓Liver fat (%) ↓ALP (U/I) ↓HbA1c (%) ↓2–hr glucose (pmol/l) ↓2–hr AUGC (mmol/l) | [47] |
Subjects | Exercise Intervention | Effects | Ref | |||
---|---|---|---|---|---|---|
Type | Frequency | Time (min) | Duration | |||
STZ-diabetic rats (single injection of STZ: 40mg/kg) | Aerobic exercise | 5 days/wk | 60 min/day | 12 wks | ↑Ejection fractions (%) ↑Left ventricular end-systolic volume ↓Serum cTn-I levels ↓Apoptotic myocardial cells ↓GRP78, CHOP, cleaved caspase-12 protein | [9] |
Obese diabetic mice (db/db) | Aerobic Exercise | 5 days/wk | 330m run at speed of 10 m/min (2 wks) + 330m run at speed of 11 m/min (3 wks) | 5 wks | ↑Body weight (gm) ↑Mean blood pressure (mmHg) ↑Heart weight (gm) ↑Blood glucose (mg/dL) ↑Stroke volume (µL) ↑Ejection fraction (%) ↑Fractional Shortening (%) | [65] |
STZ-diabetic rats (single injection of STZ: 55 g/kg) | Aerobic Exercise | 5 days/wk | 10–15 min/day, total 60 min (speed 2m/min at grade 5%) | 7 wks | ↑Citrate synthase activity (µmol/tissue(g)/min) ↑Heart Rate (bpm) ↓Left ventricular end diastolic diameter & Left ventricular end systolic diameter (mm) ↑Fractional shortening (%) ↑Ejection fraction (%) ↑Cardiac output (ml/min) ↓QRS interval (m/sec) ↑Myocyte contractile kinetics velocity(µm/sec), extent of cell shortening (µm), and relengthening velocity (µm/sec) ↓Myocyte contractile kinetics time to 50% peak contractile velocity (m/sec) & time to 50% peak relaxation velocity (m/sec) | [63] |
7 wk old diabetic rats (Injection STZ 65 mg) | Aerobic Exercise | 5 days/wk | 60 min/day (20 m/min pace) | 9 wks | ↑Cytoplasmic area (% of intracellular area) ↑Lipid droplets(µm2) ↑Mitochondria area, myofibrillar area, mitochondria quality index, cytoplasm area, and collagen fiber circumference | [69] |
3 month old male Sprague Dwaley rat (Single dose of alloxan; 200 mg/kg) | High intensity of Aerobic Exercise | 5 days/wk | NA | 4 wks | ↓Body weight (g) ↑Plasma glucose (mg/dL) ↑NOX2 & NOX4, p67phox ↓SERCA2 ↓eNOS & BH4 | [64] |
BBDR (Biomedical Research Models) male rats | Aerobic Exercise | 5 days/wk | 50 min/day | 8 wks | ↑Plasma glucose (mg/dl) & HbA1c (%) ↑LV end-systolic volume (µl), LV end-diastolic volume (µl), and LV – dp/dt (mmHg/s) ↑Myocardial mitochondria fractional area (%) | [54] |
Adult Sprague-dawley male rats + doxorubicin (DOX: 20 mg/kg body weight) | Aerobic Exercise | 5 days/wk | 60 min/day (30 m/min) | NA | ↑Protect against Dox-mediated damage in mitochondria ↓Caspase 3 & calpain ↑SOD1, SOD2, Catalase, GPX1, catalase, and HSP72 ↓Hydrogen peroxide (pmol/mg/min) | [109] |
8 wks old female C57BL6 mice | Aerobic Exercise + Resveratrol supplementation | 5 days/wk | 30 min/day | 8 wks | ↑Left ventricle posterior wall (mm) ↑Intraventricular septum (mm) ↑Left ventricle internal dimension (mm) ↑Fractional shortening ↓Citrate synthase activity (mmol/mg/min) ↓ANF & UCP3 | [110] |
Sprague-dawley (SD) diabetic rats | Aerobic Exercise | 5 days/wk | 60 min/day Low intensity: 20m/min High intensity: 34 m/min | 12 wks | ↓Left ventricular & diastolic volume ↓caspase 3, cTn-1 (lg/l), Grp78, CHOP, and Caspase 12 | [9] |
Sprague-Dawley rats (intravenous injection of streptozotocin: 60mg/kg | Aerobic Exercise | 5 days/wk | 60 min/day (32 m/min) | 10 wks | ↓Body weight (g) ↓Glucose (mmol/L) ↓Triglycerides (mmol/L) ↑Glucose oxidation (nmol/g/min) ↑Glycolysis (nmol/g/min) ↑Aortic flow (ml/min) | [33] |
6-8 wk male Wistar rat + Doxorubicin (20 mg/kg) | Aerobic Exercise | 5 days/wk | 60 min/day | 14 wks | ↑Mitochondrial respiration, calcium tolerance, oxidative damage, and heat shock proteins ↓State 3 respiration, respiratory control ratio, uncoupled respiration, aconitase activity, and protein sulfhydryl content | [72] |
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Seo, D.Y.; Ko, J.R.; Jang, J.E.; Kim, T.N.; Youm, J.B.; Kwak, H.-B.; Bae, J.H.; Kim, A.H.; Ko, K.S.; Rhee, B.D.; et al. Exercise as A Potential Therapeutic Target for Diabetic Cardiomyopathy: Insight into the Underlying Mechanisms. Int. J. Mol. Sci. 2019, 20, 6284. https://doi.org/10.3390/ijms20246284
Seo DY, Ko JR, Jang JE, Kim TN, Youm JB, Kwak H-B, Bae JH, Kim AH, Ko KS, Rhee BD, et al. Exercise as A Potential Therapeutic Target for Diabetic Cardiomyopathy: Insight into the Underlying Mechanisms. International Journal of Molecular Sciences. 2019; 20(24):6284. https://doi.org/10.3390/ijms20246284
Chicago/Turabian StyleSeo, Dae Yun, Jeong Rim Ko, Jung Eun Jang, Tae Nyun Kim, Jae Boum Youm, Hyo-Bum Kwak, Jun Hyun Bae, Amy Hyein Kim, Kyung Soo Ko, Byoung Doo Rhee, and et al. 2019. "Exercise as A Potential Therapeutic Target for Diabetic Cardiomyopathy: Insight into the Underlying Mechanisms" International Journal of Molecular Sciences 20, no. 24: 6284. https://doi.org/10.3390/ijms20246284