Volume 26, Issue 1 (Winter 2019)                   Intern Med Today 2019, 26(1): 68-81 | Back to browse issues page

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Salehi A, Abbaszadeh H, Farzanegi P. The Effect of Periodic Exercise and Resveratrol Supplementation on the Expression of Pparg Coactivator-1 Alpha and Pyruvate Dehydrogenase Kinase Genes in Gastrocnemius Muscle of Old Rats With Type 2 Diabetes. Intern Med Today 2019; 26 (1) :68-81
URL: http://imtj.gmu.ac.ir/article-1-3301-en.html
1- Department of Exercise Physiology, Sari Branch, Islamic Azad University, Sari, Iran.
2- Department of Exercise Physiology, Sari Branch, Islamic Azad University, Sari, Iran. , h.abaszade61@gmail.com
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1. Introduction

iabetes mellitus is the most common metabolic disease [2]. In diabetic patients, metabolic flexibility is impaired. Today, in addition to various sports exercises, other non-pharmacological solutions of plant origin have been considered for the management of diabetes [13, 14]. Wang et al. [12] found that those who did not exercise had a 2.2-fold increase in the expression of Pyruvate Dehydrogenase Kinase (PDK4) following resistance exercise and symmetric endurance exercise compared to single-mode endurance exercise. Sin et al. [19], by reviewing the anti-glycemic mechanism of Resveratrol in skeletal muscle of aged and diabetic patients, confirmed the changes in the expression of PDK4 through the Pparg Coactivator-1 Alpha (PGC-1α) pathway following Resveratrol consumption. The aim of present study was to examine the effect of periodic exercise and resveratrol supplementation on the expression of PDK4 and PGC-1α genes in gastrocnemius muscle of old rats with type 2 diabetes.

2. Methods and Materials

This is an experimental study conducted in 2018 in the research center of Islamic Azad University of Sari branch. 42 male rats (mean age=40-50 weeks; mean body weight=250-300 g) were randomly divided into 6 groups: healthy-control, diabetic-control, Diabetic+Periodic Exercise, Diabetic+Supplement, Diabetic+Periodic Exercise+Supplement, and Saline. The type 2 diabetes was induced by intraperitoneal injection of Streptozotocin (50 mg/kg body weight).

The exercise protocol consisted of 10 sets of 1-min activities at 50% intensity and a 2-min rest period between sets, and each week the speed was increased by 2 meters per minute. The exercises were performed for eight weeks. Resveratrol supplement was injected intraperitoneally daily at a dose of 20 mg/kg body weight. The expressions of PDK4 and PGC-1α in the gastrocnemius muscle were measured by real time Polymerase Chain Reaction (PCR) method. After quantification, gene expression values were analyzed using 2-∆∆Ct formula.

3. Results

According to the results shown in Figure 1, the highest expression level of PDK4 gene in gastrocnemius muscle was observed in the diabetic group received both periodic exercise and Resveratrol supplement and the lowest level was reported in the diabetic-control and saline groups.

The increase in PDK4 level in the rats treated with a combination of resveratrol and periodic exercise was significantly higher than that of those received resveratrol and periodic exercise alone (P<0.001). The results also show that the highest expression of PGC-1α gene was in the diabetic group received both periodic exercise and Resveratrol supplement and its lowest levels in the diabetic-control group (Figure 2). The increase in PGC-1α level in the rats treated with a combination of resveratrol and periodic exercise was significantly higher than that of those received resveratrol and periodic exercise alone (P <0.001).

4. Discussion

A number of previous studies have shown that diabetes is associated with an increase in the concentration of PDK4, a decrease in its gene expression, and its poor function [9, 11, 24]. In the present study, we found that the expression of the PDK4 gene in diabetic rats increased after administration of resveratrol to the gastrocnemius muscle tissue. Similarly, previous studies have shown that resveratrol supplementation can improve the complications of muscle aging and insulin resistance [13, 19].

Resveratrol supplementation can also increase the transactivation of PDK4 in response to decreased protein content of PDK4 [19]. In the present study, it was also observed that mRNA expression of PDK4 was higher in the resveratrol supplementation+periodic exercise group than in diabetic and saline groups. Wang et al. showed that after exercise, mRNAs associated with PGC-1α and PDK4 increased 5-8 times in both types of muscle fibers [12].

In the present study, changes in PGC-1α gene expression were consistent with the results of PDK4 gene. We suggest that a combination of resveratrol and periodic exercise be further studied as an effective way to improve glucose uptake in gastrocnemius muscles of older rats with type 2 diabetes.

5. Conclusion

The combination of resveratrol supplementation and periodic exercise can have beneficial effects on PDK4 and PGC-1α expression levels in the gastrocnemius muscle of old rats with type 2 diabetes and reduce the risks of diabetes-related complications.

Ethical Considerations

Compliance with ethical guidelines

This study was approved by the Animal Care and Use Committee of Islamic Azad University of Sari branch (Ethical Code: IR.IAU.SARI.REC.1397.011). All ethical principles governing animal experiments were fully met.


The present paper was extracted from the PhD dissertation of the first author, Department of Exercise Physiology, Sari Branch, Islamic Azad University, Sari.

Authors' contributions

Conceptualization, investigation, writing – review & editing, supervision: All Authors; Methodology, writing – original draft, resources: Ali Salehi, Hajar Abbaszadeh; Funding acquisition: Ali Salehi.

Conflicts of interest

The authors declared no conflict of interest.


The authors would like to thank the animal laboratory staff of Islamic Azad University of Sari branch for their valuable cooperation.



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Type of Study: Original | Subject: Diseases
Received: 2019/05/26 | Accepted: 2019/10/12 | Published: 2020/01/1

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