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Volume 30, Issue 1 (1-2026)
IBJ 2026, 30(1): 67-80 |
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Khosravi P, Shahidi F, Eskandari A, Khoramipour* K. Exercise-Induced Lactate Is Associated with the Modulation of Mitophagy and Ferroptosis and Reduced Amyloid-Beta and Tau in Type 2 Diabetes. IBJ 2026; 30 (1) :67-80
URL: http://ibj.pasteur.ac.ir/article-1-5311-en.html
URL: http://ibj.pasteur.ac.ir/article-1-5311-en.html
Abstract:
Background: Type 2 diabetes (T2D) is associated with increased oxidative stress, impaired mitophagy, enhanced ferroptosis, and the accumulation of amyloid beta (Aβ) and hyperphosphorylated tau in the hippocampus. Exercise-induced lactate exerts neuroprotective effects via mitochondrial quality control and redox-regulating pathways. This study investigated whether high-intensity interval training (HIIT)-induced lactate accumulation can attenuate Aβ and tau pathology in diabetic rats by modulating mitophagy and ferroptosis-related protein signaling, as it remains unclear how HIIT-induced lactate impacts these pathways in T2D.
Methods: Thirty-two male Wistar rats were assigned to control (CO), exercise (EX), diabetes (DB), and diabetes + exercise (DB+EX) groups. T2D was induced using a high-fat diet and streptozotocin (35 mg/kg). The EX and DB+EX groups performed treadmill-based HIIT (4–10 intervals at 80–100% maximum running velocity). We measured serum lactate levels and the hippocampal protein levels of MCT2, SIRT1, BDNF, p62, Keap1, NRF2, MDA, GPX4, PINK1, parkin, Aβ, and Tau using standard laboratory methods.
Results: The DB group exhibited a significant increase in hippocampal oxidative stress markers and accumulation of Aβ and Tau compared to the control groups. In contrast, the DB + EX group showed elevated serum lactate levels and higher hippocampal protein levels of MCT2, SIRT1, BDNF, p62, NRF2, GPX4, PINK1, and Parkin. This group also demonstrated reduced levels of Keap1, MDA, Aβ, and Tau relative to the DB group.
Conclusion: HIIT enhanced mitophagy and reduced ferroptosis in the hippocampus of T2D rats, coinciding with the activation of lactate-SIRT1-BDNF and p62-Keap1-NRF2 pathways and reduced Aβ and Tau accumulation.
Methods: Thirty-two male Wistar rats were assigned to control (CO), exercise (EX), diabetes (DB), and diabetes + exercise (DB+EX) groups. T2D was induced using a high-fat diet and streptozotocin (35 mg/kg). The EX and DB+EX groups performed treadmill-based HIIT (4–10 intervals at 80–100% maximum running velocity). We measured serum lactate levels and the hippocampal protein levels of MCT2, SIRT1, BDNF, p62, Keap1, NRF2, MDA, GPX4, PINK1, parkin, Aβ, and Tau using standard laboratory methods.
Results: The DB group exhibited a significant increase in hippocampal oxidative stress markers and accumulation of Aβ and Tau compared to the control groups. In contrast, the DB + EX group showed elevated serum lactate levels and higher hippocampal protein levels of MCT2, SIRT1, BDNF, p62, NRF2, GPX4, PINK1, and Parkin. This group also demonstrated reduced levels of Keap1, MDA, Aβ, and Tau relative to the DB group.
Conclusion: HIIT enhanced mitophagy and reduced ferroptosis in the hippocampus of T2D rats, coinciding with the activation of lactate-SIRT1-BDNF and p62-Keap1-NRF2 pathways and reduced Aβ and Tau accumulation.
Keywords: Ferroptosis, High-intensity interval training, Lactate, Mitophagy, Type 2 diabetes mellitus
Type of Study: Full Length/Original Article |
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