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. 2019 Dec 12;20(24):6284. doi: 10.3390/ijms20246284

Table 2.

A summary of pre-clinical studies on the preventive effects of exercise in diabetes-related cardiovascular diseases.

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]

↑, up; ↓, down; GRP78, glucose-regulated protein 78; CHOP, transcriptional induction of C/EBPhomologous protein; SSBP1; single-stranded DNA-binding protein1; PGC-1α, peroxisome proliferator-activated receptor gamma coactivator 1-alpha; NRF1, nuclear respiratory factor 1; TFAM, mitochondrial transcription factor A; TFB2M, Mitochondrial dimethyladenosine transferase 2; NOX2, NADPH oxidase 2; NOX4, NADPH oxidase 4; SERCA2, sarco/endoplasmic reticulum Ca2+-ATPase; eNOS, endothelial nitric oxide synthase; BH4, tetrahydrobiopterin; HbA1c, hemoglobin A1c; LV, left ventricle; SOD1, superoxide dismutase 1; SOD2, superoxide dismutase 2; GPX1, glutathione peroxidase 1; HSP72, heat shock protein 72; ANF, atrial natriuretic peptide; UCP3, uncoupling protein.