Resistance exercise improves cardiac function and mitochondrial efficiency in diabetic rat hearts

Abstract

Metabolic disturbance and mitochondrial dysfunction are a hallmark of diabetic cardiomyopathy (DC). Resistance exercise (RE) not only enhances the condition of healthy individuals but could also improve the status of those with disease. However, the beneficial effects of RE in the prevention of DC and mitochondrial dysfunction are uncertain. Therefore, this study investigated whether RE attenuates DC by improving mitochondrial function using an in vivo rat model of diabetes. Fourteen Otsuka Long-Evans Tokushima Fatty rats were assigned to sedentary control (SC, n = 7) and RE (n = 7) groups at 28 weeks of age. Long-Evans Tokushima Otsuka rats were used as the non-diabetic control. The RE rats were trained by 20 repetitions of climbing a ladder 5 days per week. RE rats exhibited higher glucose uptake and lower lipid profiles, indicating changes in energy metabolism. RE rats significantly increased the ejection fraction and fractional shortening compared with the SC rats. Isolated mitochondria in RE rats showed increase in mitochondrial numbers, which were accompanied by higher expression of mitochondrial biogenesis proteins such as proliferator-activated receptor-γ coactivator-1α and TFAM. Moreover, RE rats reduced proton leakage and reactive oxygen species production, with higher membrane potential. These results were accompanied by higher superoxide dismutase 2 and lower uncoupling protein 2 (UCP2) and UCP3 levels in RE rats. These data suggest that RE is effective at ameliorating DC by improving mitochondrial function, which may contribute to the maintenance of diabetic cardiac contractility.

Shengmai San Alleviates Diabetic Cardiomyopathy Through Improvement of Mitochondrial Lipid Metabolic Disorder

“…In vivo, we also detected the expression of mitochondrial UCP2, which has been suggested to be positively associated with reduced cardiac efficiency in db/db hearts [35,36]. We found that the UCP2 level was higher than in non-diabetic hearts.…”

The Role of Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Reducing Cardiovascular Events in Patients with Type 2 Diabetes

“…The precise mechanism by which hyperglycemia impairs cardiac contraction is still unknown. However, increases in free fatty acid oxidation, oxidative stress, and mitochondrial dysfunction, as well as impaired glucose utilization in cardiac myocytes, seem to be associated with poor systolic and diastolic contractile capacity, even in patients without atherosclerotic coronary artery disease [2425]. In addition, impaired microvascular endothelial function, increased myocardial fibrosis, activation of the renin-angiotensin system, and sympathetic overactivity also contribute to HF [24].…”

Physical Exercise and Its Protective Effects on Diabetic Cardiomyopathy: What Is the Evidence?

“…Ca 2+ is a key metabolic enzyme activator in mitochondria, and mitochondrial Ca 2+ circulatory balance can be easily affected by intracellular Ca 2+ homeostasis (41, 42). Resistance exercise improves cardiac function and mitochondrial efficiency in hearts, of diabetic rat, which were accompanied by higher expressions of mitochondrial biogenesis proteins such as PGC-1α and mitochondrial transcription factor A (TFAM) (45). In addition, studies have shown that high intensity exercise can increase myocardial mitochondrial contents, but no change in moderate intensity exercise (46, 47).…”