The Combined Effect of High-Intensity Interval Training and Time-Restricted Feeding on the AKT-IGF-1-mTOR Signaling Pathway in the Muscle Tissue of Type 2 Diabetic Rats

Abstract

Background/Objectives: High-intensity interval training (HIIT) and time-restricted feeding (TRF) have shown potential in enhancing glucose metabolism, increasing insulin sensitivity, and promoting muscle health. This study investigates the combined effects of HIIT and TRF on the AKT-IGF-1-mTOR signaling pathway in the muscle tissue of type 2 diabetic (T2D) rats. Methods: 42 male Wistar rats (4–5 weeks of age) were included in the study. The animals were randomly divided into two groups: 1. Standard diet (SD) non-diabetic (n = 7) and 2. High-fat diet (HFD n = 35) for 4 weeks. T2D was induced by intraperitoneal injection (IP) of streptozotocin (STZ) at 35 mg/kg. Animals with blood glucose levels ≥ 250 mg/dL were considered diabetic. Diabetic rats were randomly divided into five groups (n = 7): 1. Diabetes-HIIT (D-HIIT), 2. Diabetes-TRF (D-T), 3. Diabetes-combined TRF and HIIT (D-T+HIIT), 4. Diabetes-Untreated Control (D), and 5. Diabetes with metformin (D-MET). The HIIT protocol and TRF regimen were followed for 10 weeks. Muscle tissue was collected for histological analysis, and the expression of proteins related to the AKT-IGF-1-mTOR pathway was measured. Results: Blood glucose levels, insulin resistance (IR), and markers of muscle degradation were significantly improved in the D-T+HIIT and D-MET groups compared to the non-diabetes group. Furthermore, the activation of the AKT and mTOR signaling proteins, as well as increased IGF-1 expression, was significantly elevated in the D-T+HIIT group compared to the diabetic control group and other treatment groups, and approached levels observed in the non-diabetes group. Additionally, muscle fiber size and overall tissue structure were improved in the treatment groups, particularly in the D-T+HIIT group. Conclusions: The combination of HIIT and TRF appears to offer superior benefits in improving muscle protein synthesis, and glucose regulation in T2D rats, as compared to either HIIT or TRF alone. These findings highlight the potential of this combined approach for addressing muscle-related complications in T2D. © 2025 by the authors.