Morphological and functional characterization of diabetic cardiomyopathy in db/db mice following exercise, metformin alone, or combination treatments

The aim of the study was to explore different effects of exercise, metformin alone, or exercise combined with metformin on cardiovascular morphological and functional changes in early stage of type 2 diabetes mellitus. Eight-week-old diabetic db/db mice and BKS mice were recruited and exposed to three different treatments (exercise, metformin alone, or their combination) for 8 weeks. Metformin was administered intragastrically, and aerobic exercise was performed using treadmill with 7-12 m/min, 30-40 min/day, 5 days/week. In the combination group, aerobic exercise was carried out for 30 min after intragastric administration of metformin. The results showed that all three treatments improved cardiac fibrosis and aortic lipid deposition. Exercise intervention failed to alleviate myocardial hypertrophy, but it improved the declined heart rate and diastolic blood pressure in diabetic db/db mice. In contrast, metformin caused opposite effects in these mice. The combination of exercise and metformin had additive effects on glucose intolerance and insulin sensitivity rather than on the improvement of myocardial and aortic structure. In conclusion, metformin improved changes in the morphology and structure of the heart and aorta, while exercise alone or in combination with metformin demonstrated more advantages in cardiac functional reserve through the physiological hypertrophy of myocardium in diabetic db/db mice.