Document Type : Original Article

Authors

• Pouria Khosravi ¹
• Fereshteh Shahidi ²
• Arezoo Eskandari ²

¹ Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, Shahid Rajaee Teacher Training University, Tehran, Iran

² Department of Sports Physiology, Faculty of Physical Education and Sports Sciences, Shahid Rajaee Teacher Training University, Tehran, Iran.

Abstract

Introduction:
This study examined the effect of high-intensity interval training (HIIT) on the lactate–MCT2–GPX4–BDNF axis and its involvement in mitochondrial function and amyloid-beta (Aβ) accumulation in the hippocampus of male rats with type 2 diabetes.
Materials and Methods:
Thirty-two male Wistar rats were randomly assigned to four groups: healthy control (CO), exercise (EX), type 2 diabetes (CO+DB), and diabetes plus exercise (DB+EX). Type 2 diabetes was induced by a high-fat diet combined with streptozotocin (35 mg/kg). Training groups completed an 8-week HIIT treadmill protocol (4–10 bouts at 80–100% Vmax). Serum lactate and hippocampal MCT2, BDNF, and GPX4 protein levels were assessed using ELISA and Western blot. Normality and homogeneity were verified before analysis. Group differences were evaluated using one-way ANOVA or Kruskal–Wallis tests with appropriate post hoc analyses. Data are presented as mean ± SD (P < 0.05).
Results:
The CO+DB group showed elevated blood glucose, insulin resistance, and Aβ accumulation, along with reduced MCT2, BDNF, and GPX4 expression compared with controls (P < 0.0001). HIIT significantly increased serum lactate and hippocampal MCT2, BDNF, and GPX4 levels while decreasing Aβ accumulation in DB+EX rats (P < 0.0001), indicating enhanced mitochondrial function and antioxidant defense.
Conclusion:
HIIT stimulates lactate production and activates the MCT2–GPX4–BDNF axis, improving mitochondrial integrity and reducing neurotoxic protein accumulation in the diabetic hippocampus. These findings highlight the neuroprotective potential of HIIT against diabetes-associated cognitive decline.

Keywords:
Type 2 diabetes; High-intensity interval training (HIIT); Mitochondria; Lactate; Hippocampus; Cognitive impairment

Keywords

• Type 2 diabetes
• High-intensity interval training (HIIT)
• Mitochondria
• Lactate
• Hippocampus