Objective:To explore the effect on cardiac remodeling of combining high-intensity interval training with metformin in cases of type 1 diabetes mellitus (T1DM) and its possible mechanisms.Methods:Sixty male Sprague-Dawley rats were randomly divided into control, model, exercise, drug and combination groups with twelve per group. T1DM was induced in all except the control group using a single intraperitoneal injection of streptozotocin (60mg/kg of body weight). The control and model groups were then housed without intervention, while the drug and exercise groups underwent metformin gavage (300mg/kg/day) or 8 weeks of high-intensity interval training (3 sessions/week), respectively. The combination group receiving both. After the training, body weight, a cardiac index (heart weight/body weight), and fasting blood glucose (FBG) were measured in all of the rats. Echocardiography assessed cardiac structure and function, and myocardial tissue was collected for HE or Masson staining to measure cardiomyocyte width and collagen volume fraction respectively. Protein expression and the levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), transforming growth factor-β (TGF-β), collagen (Col), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), phosphorylated AMP-activated protein kinase (p-AMPK), ryanodine receptor (RyR), and sarcoplasmic reticulum calcium ATPase (SERCA) were determined using western blotting.Results:Compared with the control group, the model group showed significantly increased cardiac indices, FBG levels, and left ventricular end-systolic and end-diastolic diameters. But they had significantly decreased body weight, left ventricular fractional shortening and ejection fraction. Compared with the control group, there was a significant increase in the cardiomyocyte width and collagen volume fraction, as well as in ANP, BNP, TGF-β, and Col levels in the model group, along with downregulated PGC-1α, p-AMPK, RyR, and SERCA protein expression. Compared with the model group, the exercise, drug, and combination groups exhibited varying degrees of improvement in all these indicators, with the most pronounced effects in the combination group.Conclusions:High-intensity interval training combined with metformin promotes cardiac remodeling in T1DM rats, outperforming either intervention alone. The mechanism may involve minimizing myocardial fibrosis and pathological hypertrophy, restoring mitochondrial function and intracellular calcium homeostasis.

Objective:To explore the effect on cardiac remodeling of combining high-intensity interval training with metformin in cases of type 1 diabetes mellitus (T1DM) and its possible mechanisms.Methods:Sixty male Sprague-Dawley rats were randomly divided into control, model, exercise, drug and combination groups with twelve per group. T1DM was induced in all except the control group using a single intraperitoneal injection of streptozotocin (60mg/kg of body weight). The control and model groups were then housed without intervention, while the drug and exercise groups underwent metformin gavage (300mg/kg/day) or 8 weeks of high-intensity interval training (3 sessions/week), respectively. The combination group receiving both. After the training, body weight, a cardiac index (heart weight/body weight), and fasting blood glucose (FBG) were measured in all of the rats. Echocardiography assessed cardiac structure and function, and myocardial tissue was collected for HE or Masson staining to measure cardiomyocyte width and collagen volume fraction respectively. Protein expression and the levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), transforming growth factor-β (TGF-β), collagen (Col), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), phosphorylated AMP-activated protein kinase (p-AMPK), ryanodine receptor (RyR), and sarcoplasmic reticulum calcium ATPase (SERCA) were determined using western blotting.Results:Compared with the control group, the model group showed significantly increased cardiac indices, FBG levels, and left ventricular end-systolic and end-diastolic diameters. But they had significantly decreased body weight, left ventricular fractional shortening and ejection fraction. Compared with the control group, there was a significant increase in the cardiomyocyte width and collagen volume fraction, as well as in ANP, BNP, TGF-β, and Col levels in the model group, along with downregulated PGC-1α, p-AMPK, RyR, and SERCA protein expression. Compared with the model group, the exercise, drug, and combination groups exhibited varying degrees of improvement in all these indicators, with the most pronounced effects in the combination group.Conclusions:High-intensity interval training combined with metformin promotes cardiac remodeling in T1DM rats, outperforming either intervention alone. The mechanism may involve minimizing myocardial fibrosis and pathological hypertrophy, restoring mitochondrial function and intracellular calcium homeostasis.