Changes in Hepatocyte p53 Gene Expression and Insulin Resistance Index in Obese Diabetic Rats after Interval Training and N-Chromosomal Royal Jelly

Type 2 diabetes is the most common endocrine disease that occurs due to glucose intolerance due to imbalance between reserves and insulin demand. For the treatment of hyperglycemia and its side effects in diabetic patients, despite extensive research, the causes of this metabolic disorder are still not well understood at the molecular level. Some studies have reported that strenuous exercise leads to apoptosis in rat intestinal lymphocytes in rats, but exercising voluntarily on a treadmill reduces apoptosis. Induction or inhibition of apoptosis is still questionable. One of the ways of treatment and prevention is regular physical activity for patients. But what kind of sport and with what kind of protocol is a question that researchers are always looking for. Considering the role of exercise and sports activities in the prevention and control of obesity and diabetes, adopting different training methods to prevent and reduce the prevalence of obesity and also help reduce the process of obesity and its complications such as cardio metabolic diseases such as fatty liver and diabetes and etc. is necessary in studies. In traditional medicine, herbal and traditional medicines are used to prevent and treat metabolic diseases such as diabetes and fatty liver. Royal Jelly is a yellowish-white substance secreted by the submandibular glands of worker bees and consumed by queen bees throughout life and larvae during the growing season. Royal gel (RJ) and its bioactive compounds have a wide range of drugs due to their antioxidant effects and antibacterial, anti-diabetic, anti-cancer, anti-inflammatory, anti-hypertensive, and immune system properties. Also plays an important role in protecting the liver and kidneys, and in diabetic patients, it showed a decreasing effect on blood sugar and a decrease in lipid peroxidation levels and an increase in the activity of antioxidant enzymes such as CAT, GSH-PX and SOD. As p53 is a tumor-inhibiting gene that is more closely associated with cancer, however, recent research shows the vital role of p53 in the development of diabetes, how p53 signaling can serve as a potential new therapeutic target for diabetes and Operate related metabolic disorders. The P53 gene, a tumor suppressor gene that mutates and inactivates a wide range of cancers, has been dubbed the "genome protector", but new research has shown that it has profound effects on metabolism. Its activation can lead to obesity and type 2 diabetes, which is why the gene has been dubbed the "protector against obesity". While the role of this gene has been well known for decades in cancer research, little is known about its role in metabolism. Previous studies have shown that the role of P53 in metabolism is essential in its function in suppressing tumors. This gene also has effects on heart disease, obesity and type 2 diabetes. The aim of this study was to study changes in p53 gene expression in liver tissue and insulin resistance index after HIIT and Royal Jelly in obese type 2 diabetic rats.

The statistical subject of the present study consisted of wistar rats. After 20 weeks of high-fat diet, rats became diabetic by intraperitoneal injection of 25 mg STZ per kg body weight. Mice with fasting glucose between 150 and 400 mg /dL were considered to have type 2 diabetes. Mice were treated in 4 groups: 6-head diabetic control, 8-period periodic training, 7-head Royal Jelly, 8-head Periodic Exercise, and 8-head Royal Jelly training group and training protocol and gel-royal gavage. The HIIT protocol consisted of eight weeks of aerobic exercise, five sessions per week with a gradual increase in extreme frequency from 22 to 38 meters per minute and a rest period of 16 to 22 meters per minute for 15 to 34 minutes by running on a treadmill. Running time increased from 16 minutes in the first week to 34 minutes in the eighth week. At the end of the training period and 48 hours after the last training session, the experimental training groups and after 12 hours of fasting, the rats were anesthetized and sacrificed by ether anesthetic. Blood samples were collected from the heart. Glucose was measured using an auto-analyzer. Insulin measured by a special kit of Pars Azmoun Company. The insulin resistance index was calculated using the formula and gene expression was also determined by RT-PCR. To describe the data, descriptive statistics and inferential statistics of one-way analysis of variance and Bonferroni post hoc test were used to compare the differences between groups and two-factor analysis of variance and effect size index were used to compare the effect of each of the independent variables. Significance level it was considered p≤0.05.

Data analysis using one way and two-way analysis of variance test showed that:1. Mean glucose concentration (mg /dL) in the exercise group compared to the control was significantly reduced (P = 0.005) and in the exercise-royal gel group compared to the royal gel group had no significant difference and had a significant decrease compared to the control in the gel exercise group. (P = 0.001)2. Mean insulin concentration (IUI / ml) in the exercise group was significantly increased compared to the control (P = 0.005) but the royal jelly group had a significant increase compared to the control. In the exercise group, Royal Jelly had a non-significant increase compared to control.3. The mean insulin resistance index in the exercise group was significantly lower than the control group and Royal jelly (P = 0.044) 4. Mean P53 gene expression showed that, HIIT reduced P53 gene expression in hepatocytes compared with controls (P <0.001). HIIT and Royal Jelly also reduced P53 gene expression in hepatocytes compared with the control group.

Results shown that HIIT and Royal Jelly also reduced P53 gene expression in hepatocytes compared with the control group.
In general, according to the research results, it can be concluded that HIIT as well as interaction with Royal Jelly can reduce the expression of P53 gene and improve glucose levels due to the effect of genetic components effective in the release of hepatic glucose and in Type 2 diabetic patients are effective, although the results showed that the correlation coefficient between changes in insulin resistance index and P53 gene expression was not significant in the experimental groups. Royal jelly due to various vitamin and protein compounds and phenolic compounds and good substitutes for the role of glucose, as well as various antioxidant and anti-inflammatory roles, etc., regulates carbohydrate metabolism, especially glucose, and regulates lipid metabolism and reduces hyperglycemia and dyslipidemia. And reduce insulin resistance and prevent oxidative stress and inflammatory responses in people with type 2 diabetes, which is associated with exercise-related diabetes and is usually associated with overweight and obesity, but Royal Jelly alone cannot be used in these areas. And changes in the P53 gene are effective, and the use of aerobic exercise programs such as interval training can improve its effectiveness, however, further studies are needed in this area.