The effect of simultaneous intervention of Aerobic training and Berberine supplementation on AMPK and GLUT4 gene expression in the quadriceps muscle of diabetic male rats

Diabetes is a metabolic disease associated with increased blood glucose. Based on the results of previous research, physical activity, and herbal supplements containing antioxidants and anti-inflammatory agents play an important role in controlling blood glucose in diabetics. GLUT4 as a glucose transporter and AMPK as an insulin-independent biological pathway play an important role in energy homeostasis in the body. This study aimed to investigate the simultaneous intervention of aerobic training and berberine supplementation on GLUT4 and AMPK gene expression in the quadriceps muscle of diabetic male rats.

In this experimental research, 35 male Wistar rats (age 8 weeks, weight 242.15±10.32 grams) were purchased from the Pasteur Institute of Iran and transferred to the animal house located in the international campus of Yazd University of Medical Sciences. Became Rats were randomly divided into five groups of seven: 1. healthy control, 2. diabetic control, 3. diabetes + berberine, 4. diabetes + aerobic training, 5. diabetes + aerobic training + berberine. Induction of diabetes was done by one-step intraperitoneal injection of STZ (60 mg/kg). Blood glucose above 300 mg/dL meant successful induction of diabetes. The training groups worked on the treadmill according to the protocol for six weeks and with a frequency of five days a week, with a gradual increase in speed and time. Berberine supplementation with a dose of 50 mg per kilogram of body weight was done by gavage on all days and one hour before training. 48 hours after the last training session, rats were deeply anesthetized by intraperitoneal injection of ketamine (75 mg/kg body weight) and xylazine (10 mg/kg body weight) and then Sampling of quadriceps muscle tissue was done. RT-PCR technique was used to investigate the relative expression changes of GLUT4 and AMPK genes. The data were analyzed using SPSS software by one-way analysis of variance and Tukey's post hoc test at a significant level (P<0.05).

AMPK and GLUT4 gene expression in the quadriceps muscle of the diabetic control group was significantly decreased compared to the healthy control group (p=0.0001). Also, the results showed that the content of AMPK and GLUT4 gene expression in (diabetes + aerobic training) and (diabetes + aerobic training + berberine) groups increased significantly compared to the diabetic control group (p=0.0001). This increase in gene expression was higher in the (diabetes + aerobic training + berberine) group than in the (diabetes + aerobic training) group. Also, the level of AMPK and GLUT4 gene expression in the group of (diabetes + aerobic training + berberine) increased significantly compared to the group of (diabetes + berberine) (P<0.005). In the (diabetes + berberine) group compared to the diabetic control group, despite the increase in gene expression of these two variables, it was not statistically significant (P>0.05).

The simultaneous intervention of aerobic training and berberine supplementation has positive synergistic effects on AMPK and GLUT4 gene expression in the quadriceps muscle of type 1 diabetic rats and may improve energy homeostasis in the body.