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Effects of Aerobic Exercise at Different Circadian Phases on p53 Expression and β-Cell Survival in the Pancreas of Type 2 Diabetic NMRI Mice

Authors
Fatemeh Sepehrinya 1 iD
Asma Taheri 3 iD
Masoumeh Hosseinzadeh 4 iD
Affiliations
1Graduate of Exercise Physiology, Shahid Chamran University of Ahvaz, Iran
2Assistant Professor, Department of Sport Physiology, Faculty of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
3Assistant Professor, Department of Sports Physiology, Faculty of Sports Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
4Instructor, Department of Sport Physiology, Faculty of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
Overview

Abstract

Circadian rhythms regulate glucose homeostasis, insulin secretion, mitochondrial function, and apoptosis in pancreatic β-cells. The tumor suppressor gene p53 is a key molecular regulator of apoptosis and may contribute to β-cell loss in type 2 diabetes (T2DM). This study investigates the effects of aerobic exercise performed during different circadian phases on blood glucose, β-cell survival, insulin presence, and p53 gene expression in type 2 diabetic NMRI mice.  Thirty male NMRI mice were assigned to six groups: healthy controls (CH-ZT3, CH-ZT15), diabetic controls (CD-ZT3, CD-ZT15), and diabetic exercise groups trained in light (TD-ZT3) or dark phase (TD-ZT15). T2DM was induced via high-fat diet plus low-dose streptozotocin. Aerobic training (50–60% Vmax) was performed for 8 weeks. Pancreatic tissues were analyzed for β-cell survival, insulin immunostaining, and p53 expression via qRT-PCR. Data were evaluated using two-way ANOVA. Exercise significantly reduced glucose levels (p < 0.05), increased β-cell survival (p < 0.0001), and decreased p53 expression (p < 0.0001). Light-phase training (ZT3) produced greater improvements than dark-phase training. A significant interaction between training × circadian phase was found for β-cell percentage and p53 expression (p < 0.01). Aerobic exercise improves β-cell viability and reduces apoptotic signaling in diabetic mice, with circadian phase strongly modulating the benefits. Exercise during the light phase showed superior outcomes, suggesting that timing of physical activity may be an important factor in diabetes management.

Circadian Rhythm, Aerobic Exercise, Type 2 Diabetes, p53 Gene Expression, Pancreatic β-Cells, NMRI Mice

Conclusion

Aerobic exercise substantially improves β-cell survival, reduces p53-mediated apoptotic stress, and enhances glycemic control in type 2 diabetic mice. Crucially, these effects are significantly modulated by circadian timing, with light-phase exercise producing superior outcomes. Incorporating circadian strategies into exercise prescriptions may enhance therapeutic efficacy for individuals with T2DM. These findings highlight the potential of Chrono-exercise as a targeted, non-pharmacological intervention to protect β-cell function and mitigate diabetes progression.

Acknowledgements

We hereby express our gratitude to all members of the research team and technicians at Avin Stem Gen Bio Health, whose expertise and collaboration played a crucial role in the completion of this study.

Conflict of Interest

The authors declare that there is no conflict of interest.

Author Contributions

F. Sepehrinya and M. Janbozorgi conceived the study. Methodology was designed by F. Sepehrinya and A. Taheri. Data curation and investigation were performed by A. Taheri and M. Hosseinzadeh. Formal analysis and drafting of the initial manuscript were carried out by F. Sepehrinya. Manuscript review and editing were completed by M. Janbozorgi and A. Taheri. Project supervision and administration were provided by M. Janbozorgi. All authors reviewed and approved the final version of the manuscript.

Ethical Cosidreation:

The conduct and procedures involving animal experiments were approved by the Committee for Ethics in Animal Experiments at Shahid Chamran University (License number: IR.SCU.TEC.1404.062).

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