نوع مقاله : علمی - پژوهشی
نویسندگان
گروه فیزیولوژی ورزشی ، دانشکده علوم ورزشی، دانشگاه شهید چمران اهواز، اهواز، ایران
چکیده
کلیدواژهها
موضوعات
عنوان مقاله [English]
نویسندگان [English]
Background and Objective:
Type 2 diabetes mellitus is a prevalent metabolic disorder characterized by insulin resistance, impaired glucose homeostasis, increased oxidative stress, and mitochondrial dysfunction, all of which contribute to the development of diabetic cardiomyopathy. Alterations in key molecular signaling pathways involved in energy metabolism and cellular stress responses play a critical role in diabetes-related cardiac dysfunction. Among these pathways, the SIRT1–FOXO–mTOR signaling axis has gained increasing attention due to its central role in regulating mitochondrial biogenesis, autophagy, oxidative stress defense, and cell survival. Dysregulation of this pathway has been reported in diabetic conditions. High-intensity interval training (HIIT) is considered an effective non-pharmacological intervention for improving metabolic health and insulin sensitivity; however, the molecular mechanisms underlying its cardioprotective effects in type 2 diabetes remain incompletely understood. Therefore, the present study aimed to investigate the effects of HIIT on the expression of genes and proteins involved in the SIRT1–FOXO–mTOR signaling pathway in the cardiac tissue of type 2 diabetic mice.
Materials and Methods:
In this experimental study, forty adult male NMRI mice were randomly allocated into four groups: healthy control, healthy training, diabetic control, and diabetic training. Type 2 diabetes was induced by feeding a high-fat diet followed by a single intraperitoneal injection of streptozotocin (20 mg/kg). The training groups performed HIIT five days per week for eight weeks at intensities corresponding to 60–90% of maximal running speed (Vmax), which was determined using an incremental treadmill test. Forty-eight hours after the final training session, blood and cardiac tissue samples were collected. Insulin resistance was assessed using the homeostatic model assessment of insulin resistance (HOMA-IR). The expression of SIRT1 protein and FOXO and mTOR genes in cardiac tissue was evaluated using Western blotting and real-time quantitative PCR, respectively. Statistical analyses were performed using one-way analysis of variance (ANOVA) followed by Tukey’s post-hoc test, with statistical significance set at P < 0.05.
Results:
The results demonstrated that HIIT significantly increased SIRT1 protein expression and FOXO gene expression in the cardiac tissue of diabetic mice compared with diabetic control animals (P < 0.05). In contrast, mTOR gene expression was significantly reduced in the diabetic training group, indicating a downregulation of this anabolic signaling pathway. Moreover, HOMA-IR values were significantly lower in the diabetic training group, reflecting an improvement in systemic insulin sensitivity. No significant differences were observed in the measured molecular or metabolic parameters between the healthy control and healthy training groups.
Conclusion:
In conclusion, the findings of this study suggest that high-intensity interval training favorably modulates the SIRT1–FOXO–mTOR signaling pathway in the cardiac tissue of type 2 diabetic mice. The upregulation of SIRT1 and FOXO, along with the downregulation of mTOR, was accompanied by improved insulin sensitivity, indicating a potential cardioprotective mechanism of HIIT in diabetic conditions. These results highlight the therapeutic potential of HIIT as a non-pharmacological strategy for mitigating diabetes-induced molecular and metabolic abnormalities in the heart and provide a mechanistic basis for future translational and clinical studies.
کلیدواژهها [English]
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