Background and Objectives: Physical exercise is an important therapeutic modality for treating and managing diabetes. High-intensity interval training (HIIT) is considered one of the best non-drug strategies for preventing and treating type 2 diabetes mellitus (T2DM) by improving mitochondrial biogenesis and function. This study aimed to determine the effects of 12 weeks of HIIT training on the expression of tumor suppressor protein-p53, mitochondrial cytochrome c oxidase (COX), and oxidative stress in patients with T2DM. Methods: A total of thirty male sedentary patients aged (45-60 years) were diagnosed with established T2DM for more than five years. Twenty healthy volunteers, age- and sex-matched, were included in this study. Both patients and control subjects participated in the HIIT program for 12 weeks. Glycemic control variables including p53 (U/mL), COX (ng/mL), total antioxidant capacity (TAC, nmole/µL), 8-hydroxy-2'-deoxyguanosine (8-OHdG, ng/mL), as well as genomic and mitochondrial DNA content were measured in both the serum and muscle tissues of control and patient groups following exercise training. Results: There were significant improvements in fasting glucose levels. HbA1c (%), HOMA-IR (mUmmol/L2), fasting insulin (µU/mL), and C-peptide (ng/mL) were reported in T2DM and healthy controls. A significant decrease was also observed in p53 protein levels. COX, 8-OhdG, and an increase in the level of TAC were reported in T2DM following 12 weeks of HIIT exercise. Before and after exercise, p53; COX, mt-DNA content, TAC, and 8-OhdG showed an association with diabetic control parameters such as fasting glucose (FG), glycated hemoglobin (HbA1C, %), C-peptide, fasting insulin (FI), and homeostatic model assessment for insulin resistance (HOMA-IR) in patients with T2DM. These findings support the positive impact of HIIT exercise in improving regulation of mitochondrial biogenesis and subsequent control of diabetes through anti-apoptotic and anti-oxidative pathways. Conclusions: A 12-week HIIT program significantly improves diabetes by reducing insulin resistance; regulating mitochondrial biogenesis; and decreasing oxidative stress capacity among patients and healthy controls. Also; p53 protein expression; COX; 8-OhdG; and TAC and mt-DNA content were shown to be associated with T2DM before and after exercise training.
Keywords: cytochrome c oxidase; diabetes; high-intensity interval training (HIIT); mitochondria DNA (mt-DNA); oxidative stress; p53.