نوع مقاله : مقاله پژوهشی
عنوان مقاله English
نویسندگان English
Introduction and Purpose: Type 2 diabetes mellitus is a chronic metabolic disease characterized by persistent hyperglycemia, insulin resistance, and impaired function of pancreatic beta cells. Considering the important role of AMP‑activated protein kinase (AMPK) in regulating glucose uptake and improving insulin function, activation of this pathway may be an effective approach for improving glucose and lipid metabolism and reducing insulin resistance. Therefore, the present study aimed to investigate the effect of eight weeks of aerobic training on serum insulin concentration and AMPK levels in Soleus Muscle tissue of diabetic male rats.
Materials and Methods: In this experimental study, 16 male Wistar rats that were rendered diabetic using streptozotocin were randomly assigned to two groups: diabetic control (CD) and aerobic training (AT). The training protocol consisted of eight weeks of aerobic exercise on a treadmill, five sessions per week. At the end of the intervention period, serum insulin concentration and AMPK levels in muscle tissue were measured using the ELISA method. Normality of the data was assessed using the Shapiro–Wilk test and homogeneity of variances using Levene’s test. Data were analyzed using the independent t‑test.
Results: The results showed that eight weeks of aerobic training significantly increased body weight (p=0.001) and AMPK (p=0.001) and significantly decreased blood glucose (p=0.001) and insulin levels (p=0.002) in the aerobic training group (AT) compared with the diabetic control group (CD) (P<0.05).
Conclusion: The findings of this study indicate that aerobic training, by increasing AMPK and reducing blood glucose and insulin levels, can have beneficial effects on metabolic indicators in an animal model of type 2 diabetes. In addition, the increase in body weight observed in the training group compared with the diabetic control group may indicate a partial attenuation of diabetes‑induced metabolic complications. However, generalization of these findings to humans requires further clinical studies.
کلیدواژهها English
1. Introduction and Objective
Type 2 diabetes mellitus (T2DM) is a prevalent chronic metabolic disorder characterized by persistent hyperglycemia, insulin resistance, and impaired pancreatic β-cell function. Global projections estimate a rise in affected individuals from approximately 425 million in 2017 to over 629 million by 2045. AMP-activated protein kinase (AMPK) is a key cellular energy sensor involved in regulating glucose and lipid homeostasis. It is recognized as an important therapeutic target for improving insulin resistance and enhancing glucose uptake. AMPK activation increases glucose transporters (GLUT1 and GLUT4), improves insulin sensitivity, reduces β-cell apoptosis, and regulates both catabolic and anabolic metabolic pathways, thereby playing a crucial role in maintaining energy homeostasis. Aerobic exercise, a non-pharmacological intervention, can improve insulin sensitivity and modulate cellular signaling pathways involved in blood glucose regulation and metabolic control. However, evidence regarding the precise role of AMPK activation in exercise-induced glucose uptake remains somewhat inconsistent.
Therefore, the present study aimed to investigate the effect of eight weeks of aerobic training on serum insulin concentration and AMPK levels in the muscle tissue of male rats with type 2 diabetes.
2. Materials and Methods
This basic experimental research adhered to the ethical principles approved by the Animal Ethics Committee of the Islamic Azad University, Neyshabur Branch (Code: IR.IAU.NEYSHABUR.REC.1404.034). Sixteen eight-week-old male Wistar rats, with an initial body weight of 200 ± 15 g, were housed under standard laboratory conditions (12:12 h light–dark cycle, 22 ± 3°C, and 40–60% relative humidity). To induce type 2 diabetes, animals were fed a high-fat diet for four weeks, followed by an intraperitoneal injection of streptozotocin (STZ) at a dose of 30 mg/kg body weight. One week post-injection, diabetes was confirmed by measuring blood glucose from the tail vein; levels ≥200 mg/dL were considered diabetic. After a familiarization period with the environment and treadmill, the animals were randomly assigned to two equal groups: diabetic control (CD, n=8) and aerobic training (AT, n=8). The aerobic training protocol involved treadmill running for eight weeks, five sessions per week, structured into three phases: familiarization, overload, and maintenance. During the familiarization phase (week 1), rats ran at 15 m/min for 10–15 minutes. In the overload phase (weeks 2–3), training intensity and duration gradually increased to 25 m/min for 40 minutes. The maintenance phase (weeks 4–8) continued at 25 m/min for 40 minutes. Forty-eight hours after the final training session and following 12 hours of fasting, animals were anesthetized with ketamine (75 mg/kg) and xylazine (10 mg/kg), and blood samples were collected directly from the heart. For AMPK measurement, approximately 80 mg of soleus muscle tissue was excised, homogenized, centrifuged, and the supernatant was stored at −80°C until analysis. Serum insulin concentration and muscle AMPK levels were measured using ELISA kits from Mercodia (Germany) and Bio-Techne (USA), respectively. Data normality was assessed using the Shapiro–Wilk test, and homogeneity of variances was evaluated using Levene's test. Data were analyzed using an independent t-test in SPSS version 25, with a significance level set at P<0.05.
3. Results
Eight weeks of aerobic training significantly altered several variables in diabetic rats. The aerobic training (AT) group exhibited significantly higher body weight (205.00 ± 4.59 g) compared to the diabetic control (CD) group (139.25 ± 2.91 g, P=0.000). Fasting blood glucose levels were significantly lower in the AT group (202.00 ± 4.44 mg/dL) than in the CD group (286.37 ± 2.19 mg/dL, P=0.000). Similarly, serum insulin concentration was significantly reduced in the AT group (3.41 ± 0.192 ng/mL) compared to the CD group (3.74 ± 0.045 ng/mL, P=0.002). Furthermore, soleus muscle AMPK levels were significantly higher in the AT group (4.19 ± 0.48 kDa) than in the CD group (2.23 ± 0.53 kDa, P=0.000). Overall, significant differences (P < 0.05) were observed between the two groups for all measured variables: body weight, blood glucose, insulin, and AMPK.
The findings of the present study indicate that, in an animal model of type 2 diabetes, regular aerobic exercise is associated with increased body weight, decreased blood glucose and serum insulin levels, and increased muscle AMPK levels, collectively reflecting an improvement in metabolic status. The simultaneous reduction in glucose and insulin levels in the training group likely reflects improved insulin sensitivity in target tissues, particularly skeletal muscle. The increased AMPK level in muscle tissue also suggests activation of a key metabolic regulatory pathway in response to aerobic training. Activation of this pathway may enhance glucose uptake by promoting GLUT4 translocation to the cell membrane, increasing fatty acid oxidation, and reducing the accumulation of lipotoxic metabolites, thereby contributing to reduced insulin resistance. Therefore, aerobic exercise may contribute to the improvement of diabetes-related metabolic disturbances through multiple molecular and cellular mechanisms.
4. Conclusions
Overall, the results of this study demonstrated that eight weeks of structured aerobic training in male rats with type 2 diabetes significantly increased muscle AMPK levels and reduced blood glucose and serum insulin concentrations. Additionally, body weight in the training group was higher than in the diabetic control group. These findings suggest that aerobic exercise may serve as an effective non-pharmacological strategy for improving metabolic indicators associated with type 2 diabetes. However, due to the animal nature of this study, direct generalization of the findings to humans requires further clinical research.
5. Acknowledgment & Funding
This study did not receive any financial support and was conducted using the authors’ personal funds. The authors sincerely acknowledge the administrative support and cooperation of the Research and Technology Deputy of Islamic Azad University, Neyshabur Branch, as well as the assistance of the staff of the Exercise Physiology Laboratory and the Animal Care Facility.
6. Ethical Considerations
This study was approved by the Ethics Committee of Islamic Azad University, Neyshabur Branch, under ethics code IR.IAU.NEYSHABUR.REC.1404.034. All ethical principles and guidelines for the care and handling of laboratory animals were observed throughout the study.
7. Authors' Contributions
Mr. Hosein Ghanbari: Study design, implementation of the laboratory procedures and exercise protocol, data collection, and preparation of the initial manuscript draft; Dr. Ameneh Barjasteh Yazdi: Scientific guidance and supervision, development of the study methodology, critical review, and revision of the manuscript; Dr. Mohammadreza Hoseinabadi: Supervision and control of the statistical section, statistical analysis, and verification of the accuracy of the statistical results; Dr. Soheyla Goharrokhi: Final review of the manuscript content and scientific editing. All authors reviewed and approved the final version of the manuscript.
8. Conflict of Interest
The authors declare no conflict of interest.
