The combined effects of high-intensity interval training and time-restricted feeding on the AKT/FOXO1/PEPCK pathway in diabetic rats

High-intensity interval training (HIIT) and time-restricted feeding (TRF) have shown promise for improving glucose regulation by increasing insulin sensitivity, enhancing glucose uptake, reducing glucose production. Therefore, this study investigates the combined effects of HIIT and TRF on the AKT/FOXO1/PEPCK signaling pathway in the liver tissue of type 2 diabetic rats. 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 (Non-D, n = 7) (2) High-fat diet (HFD, n = 35) for 4 weeks. To induce diabetes, 35 mg/kg of streptozotocin (STZ) was injected intraperitoneally (IP). Animals with blood glucose levels of > 250 mg/dL were considered as diabetic. Diabetic rats were randomly divided into 5 groups (n = 7): (1) Diabetes-exercise (D-EX), (2) Diabetes-TRF (D-TRF), (3) Diabetes-combined TRF and exercise (D-TRF&EX), (4) Diabetes no treatment (D-NT), (5) Diabetes with metformin (D-MET). Interventions (HIIT and TRF) were performed for 10 weeks. Rats in the Non-D group did not exercise and did not receive metformin or TRF. Periodic Acid-Schiff (PAS) staining was used to histologically analyze the liver tissue. Levels of blood glucose, insulin resistance (IR), FOXO1 protein, PEPCK, and area under the curve (AUC) following the IPGTT test, were significantly decreased in treatment groups compared to the D-NT group (p < 0.05). The AKT protein levels (p < 0.01), glycogen content (p < 0.05), and insulin sensitivity (p < 0.001) increased in the treatment groups as compared with the D-NT group. Microscopic examination of the liver tissue in general showed a better tissue arrangement in both treatment groups than in the D-NT group. Combining HIIT and TRF may be effective for improving blood glucose regulation, insulin sensitivity, in type 2 diabetes, as compared to TRF or HIIT interventions alone.