Razi Journal of Medical Sciences

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Yeylaghi Ashrafi M R, Abednatanzi H, Ghazalian F. The effect of eight weeks of high intensity interval training and n-chromosomal royal jelly on G6Pase gene expression in hepatocytes, glucose levels and insulin resistance in type 2 diabetic rats. RJMS 2020; 27 (10) :135-150
URL: http://rjms.iums.ac.ir/article-1-6387-en.html

Background & Aims: The aim of this study was the interactive effect of High Intensity Exercise Training (HIIT) and n-chromosomal royal jelly on G6Pase gene expression in liver hepatocytes and glucose levels and insulin resistance in type 2 diabetic rats. Intense interval training is usually performed with intensities above 90% of the maximum heart rate and short rest periods and a training duration of less than 20 minutes. Royal Jelly is a yellowish white substance secreted by the submandibular glands of worker bees and by the queen bee is consumed throughout its life and the larvae during the growing period. Due to their anti-oxidant and anti-diabetic, anti-cancer, anti-inflammatory effects, various drugs are obtained from gellerial. Evidence from studies shows that the possibility of increased glucose-6-phosphatase expression plays an important role in increasing hepatic glucose production. Therefore, this article intends to report the interactive effect of HIIT and consumption of n-chromosomal royal jelly on glucose regulatory factors.
Methods: The statistical population of the present study consisted of 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 PCR. To describe the data, descriptive statistics and inferential statistics of one-way analysis of variance and Ben Foroni 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.
 Results: 1. Mean glucose concentration (mg / dL) in the exercise group (138.25) compared to the control (333.83) was significantly reduced (p= 0.005) and in the exercise-royal gel group (134) compared to the royal gel group (131.57) had no significant difference (p= 0.992) and had a significant decrease compared to the control in the gel exercise group (p= 0.001). 2. Mean mean insulin concentration (IUI / ml) in the exercise group (6.22) was significantly increased compared to the control (3.89) (P = 0.005) and in the exercise-royal gel group (5.12) compared to the royal gel group (7.36) p= 0.992) but the royal jelly group had a significant increase compared to the control. And in the exercise group, Royal Jelly had a non-significant increase compared to control. 3. The mean insulin resistance index in the exercise group (2.04) was significantly lower than the control group (3.18) and gelravial (2.31) (p= 0.044).  4. The mean ratio of G6pase gene expression in the exercise group (1.43) and in the exercise-gel-royal group (2.74) increased significantly compared to the control (1) and compared to gel-royal (0.45) but the expression of G6pase gene in the group Royal jelly decreased compared to control, but the difference was not significant.

Conclusion: Since increasing glucose production from non-carbohydrate pathways in the process of hepatic gluconeogenesis as well as accelerating the glycolysis process ultimately leads to increased hepatic glucose release, especially in diabetic patients. The findings of the present study revealed that the expression of genes involved in gluconeogenesis the liver is affected by exercise combined with royal jelly. Eight weeks of HIIT alone, in interaction with n-chromosomal royal jelly, increased G6Pase expression in the hepatocytes of type 2 diabetic rats compared with controls who did not participate in the exercise program, but the gel only decreased expression. The gene was compared to the control group. The possibility of increased liver G6Pase expression during acute exercise is due to the fact that this gene is positively regulated by prolonged fasting in rodents. On the other hand, it is also noted that insulin signaling pathways it plays an important role in controlling the expression of gluconeogenic genes such as G6Pase, which regulates the rate of hepatic gluconeogenesis. It has been suggested that G6Pase encoding is strongly mediated by transcription of some key hormones, especially insulin, glucagon, adrenaline, and glucocorticoids. Insulin is the most important regulatory factor in inhibiting gluconeogenesis and hepatic glucose production in post-meal conditions. In other words, although free fatty acids, glucocorticoids, and glucagon increase G6Pase expression, insulin strongly inhibits the expression of these genes. Based on the available evidence, the decrease in G6Pase gene expression in the Royal Jelly group can be attributed to a further increase in insulin levels in response to long-term use of Royal Jelly. Compared to the control group, intermittent aerobic exercise led to a significant reduction in glucose and insulin resistance index. Improvement of glycemic profile in response to periodic exercise and royal jelly in diabetic rats can be attributed to changes in glucose levels and beta cell function as well as changes in the expression of hepatic gluconeogenic genes.