---

Background: The mTORC1 pathway is one of the important pathways for protein synthesis in the heart, which can lead to physiological or pathological hypertrophy. Diabetes can lead to defects in this pathway. The aim of this study was to examine the effect of 4 weeks’ aerobic training on the content of mTORC1 signaling pathway proteins in heart tissue of type 1 diabetes rats.

Methods: In this experimental study, 16 Sprague-Dawley male rats (mean weight of 300 ± 20 gr) were selected and after induction of diabetes by STZ was randomly assigned into two groups: diabetic training and diabetic control. The experimental group performed HIIT training for 4 weeks’ accordance with the training program (each session 42 minutes, 10-20 m/m) for 4 weeks, while the control group did not have any training program. Dependent t-test and independent T-test were used to analyze the data
 

Results: Significant increase was observed in the content of AKT1 (p<0.015), mTOR (p<0.001), P70S6K1 (p<0.006), 4EBP1 (p<0.05) proteins in the aerobic training group compared to control group.
Conclusion: Aerobic training for 4 weeks enabled to activate the pathway AKT1/mTOR/P70S6K1 and AKT1/mTOR/4E-BP1 in mTORC1 pathway; therefore, due to cardiac complications in type 1 diabetic patients, aerobic training can lead to protein synthesis and physiological cardiac hypertrophy through mTORC1 pathway.
 

---

Background: Diabetic cardiomyopathy is a complication type 2 diabetes mellitus that can lead to cardiac muscle autophagy through the proteins FOXO3a and Beclin-1. Therefore, the aim of this study is to investigate the effect of 8 weeks High intensity interval training (HIIT) on the content of FOXO3a and Beclin-1 proteins in heart muscle tissue of Sprague-Dawley rats with type 2 diabetic rats.
Methods: In this experimental study, 12 two-month-old Sprague-Dawley rats with a mean weight of 270±20 g were selected. After diabetic induction with STZ and Nicotinamide, rats were randomly assigned to two groups, diabetic training (6 heads) and diabetic control (6 heads). The training group trained for 4 days a week in accordance with the training program (each session 42 minutes, 10-30 m/m) for 8 weeks, while the control group did not have any training program. Also, rats did not receive any insulin treatment during the study period. The independent t-test was used to analyze the data. Significance level is considered p≤0.05.
Results: Eight weeks of HIIT training resulted in a significant decrease in FOXO3a (P=0.008) and Beclin-1 (P=0.002) proteins content in diabetic training group compared to diabetic control group.
Conclusion: It can be said that eight weeks of HIIT training decreased the FOXO3a/Beclin-1 autophagy pathway by decreasing FOXO3a and Beclin-1 protein content. Therefore, the use of HIIT exercises may be useful for diabetic subjects who are prone to diabetic cardiomyopathy.

---

Background: Obesity and type 2 diabetes can impair the function of important cellular pathways. Activation of the mTOR pathway results in regulation of the SREBP1 protein for metabolism and regulation of adipose tissue. The aim of this study was to investigate the effect of 4 weeks of high intensity interval training on the content of mTOR and SREBP1 in adipose tissue of type 2 diabetic rats.
Methods: In this experimental study, 12 to 2-month-old male Sprague-Dawley rats weighing 300 20± 20 g were selected and after being diabetic by induction of STZ and nicotine amide, randomly divided in two groups, diabetic training (6 rats) and diabetic control (6 rats). Exercise group training 4 days a week for 4 weeks according to the training HIIT; The control group had no exercise program. Independent t-test and dependent t-test were used for data analysis.
Results: There was no significant change in mTOR protein content (p=0.12); But the SREBP1 protein content (p=0.001) increased significantly. The weight of control group (P=0.0001) and HIIT group (P=0.010) showed a significant increase. Blood sugar in the control group also increased significantly (P=0.0001), but HIIT mice did not show a significant change (P = 0.14).
Conclusion: 4 weeks of HIIT training did not significantly change weight, blood glucose and mTOR protein content. But it did increase the SREBP1 content, so factors such as duration and intensity of training should be adjusted in order to achieve the best results when administering HIIT.

---

Background: One of the most important biological pathways involved in maintaining energy homeostasis is the AMPK PGC-1α pathway. Activation of this pathway through exercise can be important in regulating mitochondrial biogenesis processes and maintaining energy balance in diabetics. Therefore, the aim of this study was to investigate the effect of endurance exercise on the content of AMPK and PGC-1α proteins in the left ventricular heart tissue of male rats with type 2 diabetes.

Methods: In this experimental study, 12 two-month-old Sprague-Dawley rats with a mean weight of 270±20 g were selected. After diabetic induction with STZ and Nicotinamide, rats were randomly assigned to two groups, training diabetic and control diabetic (6 heads in group each). The training group performed 4 days a week for 8 weeks, including 30 minutes of endurance training with an intensity of about 50 to 70% of the maximum speed; While the control group did not have any training program. Also, rats did not receive any insulin treatment during the study period. The independent t-test was used in SPSS software version 21 to analyze the data.

Results: A significant increase was observed in the content of AMPK (P=0.002) and PGC-1α (P=0.0001) proteins in the endurance exercise group compared to control.
Conclusion: Based on the results of the present study, endurance exercise was able to significantly increase the content of AMPK and PGC-1α proteins. Therefore, it is possible that an increasing these proteins can lead to energy production and increase mitochondrial biogenesis.

---

Background: The pathway of insulin messengers is so important that diabetes can lead to disruption of this pathway. However, the aim of this study was to investigate the effect of 8 weeks of endurance training on protein Kinase-B (PKB or AKT) and mechanical target of rapamycin (mTOR) in the left ventricle of the heart of diabetic rats induced by streptozotocin and nicotinamide.
Methods: In this experimental study, 12 head two-month-old Sprague-Dawley rats with a mean weight of 270±20 g were selected. After diabetic induction with streptozotocin and Nicotinamide, rats were randomly assigned to two groups, training and control (6 heads in group each). The rat training program was performed on a treadmill for 8 weeks and 4 sessions per week, including 30 minutes of endurance training with an intensity of about 50 to 70% of the maximum speed. SPSS software and independent t-test were used to analyze the data.
Results: Eight weeks of endurance training resulted in a significant increase in protein Kinase-B content (P=0.03); But no significant change in Protein Mechanistic Target of Rapamycin content was observed in the endurance training group compared to the control (P=0.97).
Conclusion: protein Kinase-B is a key protein for regulating many cellular pathways, which was significantly increased by eight weeks of endurance training. Due to the fact that the content of protein mechanistic target of rapamycin does not change, it is possible that endurance training cannot lead to physiological hypertrophy heart through the mTORC1 pathway.

---

Background: The myostatin/SMAD pathway is one of the most important regulatory pathways in heart muscle cells atrophy. Diabetes can disorder this pathway. Therefore, the aim of the present study was to evaluate the effect of six weeks of endurance training on the content myostatin and SMAD2/3 proteins in the left ventricular tissue of the heart muscle of type 1 diabetic rats.
Methods: In this study, 12 head 2-month-old male Sprague-Dawley male rats with a mean weight of 300±20 g were selected. After induction of diabetes through streptozotocin solution, they were randomly divided into 2 groups: diabetic endurance training (6 heads) and diabetic control (6 heads); The training groups performed the training program 4 days a week for 6 weeks, including 32 minutes of endurance training with an intensity of about 50 to 70% of the maximum speed; SPSS software version 23 and independent t-test were used to analyze the data. Significance level was considered p≤0.05.
Findings: Endurance training resulted in a significant decrease in myostatin (P=0.024) and SMAD2/3 (P=0.001) proteins content between training and control groups in myocardial tissue.
Conclusion: It can be said that endurance training by reducing the content of myostatin and SMAD2/3 proteins in the left ventricle of the heart may have been able to prevent cardiac atrophy in type 1 diabetic subjects. This reduction can lead to physiological cardiac hypertrophy.

---

Background: AMPK and P53 proteins regulate the TOR protein in the TORC1 complex, which regulates many physiological processes. The aim of this study was to evaluate the effect of AMPK and P53 proteins on the TOR pathway following endurance training in the left ventricle of the heart of diabetic rats by streptozotocin and nicotinamide.
Methods: In this experimental study, 12 head two-month-old Sprague-Dawley rats with a mean weight of 270±20 g were selected. After diabetic induction with streptozotocin and Nicotinamide, rats were randomly assigned to two groups, training and control (6 heads in group each). The training group performed endurance training on a treadmill for rodents for 6 weeks and 4 sessions per week for 42 minutes with an intensity of about 50 to 70% of the maximum speed. SPSS software version 23 and independent t-test were used to analyze the data.
Results: Six weeks of endurance training led to significant increase in the protein content of AMPK (P=0.009) and TOR (P=0.005) between training and control groups in the left ventricular tissue of the heart muscle. In contrast, a significant decrease in P53 protein content was observed between the training and control groups in the left ventricular tissue of the heart muscle (P=0.0001).
Conclusion: The results showed that endurance training can with increase the content of AMPK and TOR proteins and decrease the content of P53 protein to regulate processes such as metabolism, mitochondrial biogenesis, cardiac hypertrophy, inhibition of autophagy in the hearts of diabetic subjects.
 

---

Background: FOXO family proteins are important factors in autophagy pathway. Protein kinase-B is an important regulator for this family that can be regulated through exercise training. Therefore, the aim of this study is to investigate the effect of protein kinase-B (PKB) on FOXO autophagy family proteins (FOXO1 and FOXO3a) following high intensity interval training (HIIT) in the left ventricle of the heart of diabetic rats by streptozotocin (STZ) and nicotinamide.
Methods: In this experimental study, 12 two-month-old Sprague-Dawley rats with a mean weight of 270±20 g were selected. After type 2 diabetes induction with STZ and Nicotinamide, rats were randomly assigned to two groups, diabetic training (6 heads) and diabetic control (6 heads). The training group trained for 4 days a week in accordance with the training program for 8 weeks. SPSS software version 23 and independent t-test were used to analyze the data. Significance level is considered p≤0.05.
Results: HIIT training resulted in a significant increase in PKB protein content between training and control groups (P=0.0001). In contrast, a significant decrease in protein content of FOXO1 (P=0.003) and FOXO3a (P=0.006) was observed between the training and control groups.
Conclusion: It seems based on the results HIIT with increasing and regulating PKB leads to a decrease and inactivation of FOXO1 and FOXO3a proteins in the hearts of diabetic subjects. Inhibition of these proteins can prevent excessive cardiac autophagy in diabetic subjects.

---

Background: Diabetes is an important factor in heart defects that can lead to atrophy of heart cells. Exercise can prevent the complications of diabetes by regulating cellular factors. Therefore, the aim of the present study was to evaluate the effect of endurance and high-intensity interval training on the content MSTN and Follistatin proteins in the left ventricular tissue of the heart of type 1 and 2 diabetic rats
Methods: In this study, 36 head 2-month-old male Sprague-Dawley male rats with a mean weight of 280±30 g were selected.
After induction of type 1 (18 head) and 2 (18 head) diabetics through streptozotocin and nicotinamide solution, each type of diabetes was randomly divided into 3 groups: endurance training, HIIT and control (6 heads per group); The training groups performed endurance (50 to 70% of maximum speed) and HIIT (intensity 85 to 95% of maximum speed) training program 4 days a week for 4 weeks; Data analysis was performed by one-way ANOVA and Tukey post hoc tests in SPSS software.
Results: Endurance training and HIIT in diabetic training groups led to a significant decrease in MSTN protein content (P=0.0001) and an increase in Follistatin protein content (P=0.0001).
Conclusion: It seems that four weeks of endurance training and HIIT can prevent excessive myocardial atrophy by decreasing the MSTN content and increasing Follistatin. Therefore, exercise training with the intensity, duration and type can be a good defense and treatment mechanisms for diabetics to prevent or reduce heart complications.

---

Background: mTOR and CREB proteins are two important factors in cellular pathways and regulating fat tissue metabolism. Therefore, the aim of this research is the effect of endurance training on the amount of mTOR and CREB proteins in the adipose tissue of type 2 diabetic rats.
Methods: In this experimental study, 18 rats 2-month-old male Sprague-Dawley rats with a mean weight of 270±20g were selected. 12 rats became type 2 diabetic by intraperitoneal injection of Streptozotocin solutions. These rats were randomly divided into 2 groups: diabetic training and diabetic control (6 heads per group); A healthy control group (6 heads) was also considered. The training group practiced endurance training 4 days a week for 6 weeks. Data were analyzed using SPSS software version 23 and one-way ANOVA and Tukey post hoc tests.
Results: mTOR protein content showed a significant change after 6 weeks of endurance training (P=0.0001); Tukey's post hoc test showed that this change was significant between the pairs of diabetic training groups to healthy controls (P=0.004) and diabetic control groups to healthy controls (P=0.0001). CREB protein content showed a significant change (P=0.0001); this change was significant between the pairs of diabetic training to diabetic control groups (P=0.02), diabetic training to healthy control (P=0.0001), and diabetic control to healthy control groups (P=0.0001).
Conclusion: mTOR and CREB proteins decreased after Endurance Training, which can be effective in regulating adipose tissue metabolism; however, more training conditions should be considered.

---

Background: Endoplasmic reticulum stress leads to unfolded or folded protein response, and ATF4 and CHOP proteins play very important roles in this signalling pathway; Therefore, the aim of this research is the effect of resistance training on the content of ATF4 and CHOP proteins in the left ventricle of the heart of type 2 diabetic rats.
Methods: In this experimental study, 12 two-month-old male Sprague Dawley rats were selected and their weight reached an average of 280±20 gr after four weeks. Type 2 diabetes was induced by injecting nicotinamide solutions (110 mg/kg) and streptozotocin (60 mg/kg). The rats were randomly divided into 2 groups, resistance training and diabetic control; Resistance training consisted of 8 weeks and 3 sessions per week of climbing a vertical ladder with an 85-degree slope, one meter long with 26 steps and 2 cm space between each step. To analyze data, independent t-test was used in SPSS version 29 and Graphpad Prism version 10.2.3. A significance level of P≤0.05 is considered.
Results: The content of ATF4 and CHOP proteins after 8 weeks of resistance training showed a significant change compared to the control group in the left ventricle of the heart (P=0.001).
Conclusion: The increase of ATF4 and CHOP proteins can lead to increased cell death of cardiomyocytes in the left ventricle of the heart of type 2 diabetic subjects through increasing the endoplasmic reticulum stress and initiating the unfolded or folded protein response.

---

Background: Diabetes can disrupt the balance of cell death through different cell pathways, and exercise or consumption supplements can be effective in maintaining the balance of cell death types; Therefore, the purpose of this research is the effect of magnesium supplementation and exercise training on the content of CREB2 and C/EBP homologous protein (CHOP) in the left ventricle of the heart of type 2 diabetic rats.
Methods: In this experimental study, 24 2-month-old male Sprague-Dawley rats with an average weight of 280±20 grams were selected. Type 2 diabetes was induced by injecting nicotinamide and streptozotocin solutions. The rats were randomly divided into four groups, 1) control, 2) supplement, 3) training and 4) training+supplement; Resistance training consisted of 8 weeks and 3 weekly sessions of climbing a ladder. Magnesium supplement was given to rats once a day. To analyze the data, one-way ANOVA and Tukey's post hoc tests were used in SPSS version 29.
Results: Eight weeks of magnesium supplementation and resistance training led to a significant change in the content of CREB2 and CHOP proteins between groups in the left ventricle of the heart (P= 0.001). A significant decrease was observed in the groups of resistance training + magnesium supplement and magnesium supplement compared to the control group (P≥ 0.05); But the resistance training group had increased compared to the control group (P≥ 0.05).
Conclusion: The increase and decrease of CREB2 and CHOP proteins in the left ventricle of the heart can lead to improvement and physiological adaptation, like a bilateral mechanism.