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Peer-reviewedCC BY 4.0Frontiers in Endocrinology

Effects of high-intensity treadmill exercise on GLUT4, TNF-α, and INSIG1 mRNA expression and blood glucose levels in streptozotocin-induced diabetic rats

  • Sezgin Hepsert1
  • Semih Dalkılıç2
  • Lütfiye Kadıoğlu Dalkılıç2
  • İbrahim Aydınlı3
  • Dilek Arslan4
  • Mehmet Akif Sarı5
  • Yakup Kılıc5
5 affiliations
  1. 1Physical Education Teaching, Ministry of Education
  2. 2Department of Biology, Faculty of Science, Firat University
  3. 3Faculty of Sports Sciences, Kocaeli University
  4. 4Baskil Vacational School, Firat University
  5. 5Department of Physical Education and Sports, Fırat University
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Abstract

Background: Exercise plays a central role in diabetes management by modulating glucose homeostasis and metabolic gene networks. This study investigated the effects of a 6-week high-intensity treadmill exercise protocol on GLUT4, TNF-α, and INSIG1 mRNA expression in soleus muscle and blood glucose levels in streptozotocin (STZ)-induced diabetic rats.

Methods: In this randomized experimental study, 45 eight-week-old male Sprague-Dawley rats were allocated to Control (C), Sedentary diabetic (S), and Exercise diabetic (E) groups (n=15/group). Diabetes was induced via a single intraperitoneal STZ injection (60 mg/kg) and confirmed 72 h post-injection (blood glucose >200 mg/dL). Group E underwent treadmill exercise (30 min/day, 5 days/week, 6 weeks). Blood glucose was assessed longitudinally, and soleus muscle GLUT4, TNF-a, and INSIG1 mRNA expression levels were analyzed post-intervention via qRT-PCR.

Results: Blood glucose levels were 80.33 ± 7.79, 86.33 ± 7.94, and 88.27 ± 6.52 mg/dL at weeks 1, 3, and 6, respectively, in the C group; 356.64 ± 160.63, 361.91 ± 133.09, and 362.64 ± 116.10 mg/dL in the S group; and 452.13 ± 165.34, 376.73 ± 189.70, and 286.80 ± 145.92 mg/dL in the E group. Mixed-effects analysis revealed significant main effects of group (F(2,38) = 29.520, p < 0.001, ηp² = 0.608) and time (F(2,76) = 6.651, p = 0.022, ηp² = 0.149), and a significant group × time interaction (F(4,76) = 9.143, p < 0.001, ηp² = 0.325). Although blood glucose decreased progressively in E, post-test levels did not differ significantly between E and S. GLUT4 mRNA expression was significantly higher, whereas TNF-α mRNA expression was significantly lower in E than S (p < 0.05). No significant difference was observed in INSIG1 mRNA expression between E and S (p > 0.05).

Conclusion: A 6-week high-intensity treadmill exercise regimen was associated with significant GLUT4 upregulation and reduced TNF-α mRNA expression in soleus muscle, without significant post-intervention blood glucose differences compared with sedentary diabetic controls. These findings suggest localized transcriptional adaptations rather than restoration of systemic glucose homeostasis or superior glycemic control under STZ-induced diabetic conditions.

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Cite

BibTeXRIS
BibTeX
@article{hepsert2026effects,
  title = {{Effects of high-intensity treadmill exercise on GLUT4, TNF-α, and INSIG1 mRNA expression and blood glucose levels in streptozotocin-induced diabetic rats}},
  author = {Sezgin Hepsert and Semih Dalkılıç and Lütfiye Kadıoğlu Dalkılıç and İbrahim Aydınlı and Dilek Arslan and Mehmet Akif Sarı and Yakup Kılıc},
  journal = {Frontiers in Endocrinology},
  year = {2026},
  month = oct,
  doi = {10.3389/fendo.2026.1973677},
  url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1973677/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Effects of high-intensity treadmill exercise on GLUT4, TNF-α, and INSIG1 mRNA expression and blood glucose levels in streptozotocin-induced diabetic rats
AU  - Sezgin Hepsert
AU  - Semih Dalkılıç
AU  - Lütfiye Kadıoğlu Dalkılıç
AU  - İbrahim Aydınlı
AU  - Dilek Arslan
AU  - Mehmet Akif Sarı
AU  - Yakup Kılıc
PY  - 2026
DA  - 2026/10/08
JO  - Frontiers in Endocrinology
DO  - 10.3389/fendo.2026.1973677
UR  - https://www.frontiersin.org/articles/10.3389/fendo.2026.1973677/full
AB  - Background: Exercise plays a central role in diabetes management by modulating glucose homeostasis and metabolic gene networks. This study investigated the effects of a 6-week high-intensity treadmill exercise protocol on GLUT4, TNF-α, and INSIG1 mRNA expression in soleus muscle and blood glucose levels in streptozotocin (STZ)-induced diabetic rats.  Methods: In this randomized experimental study, 45 eight-week-old male Sprague-Dawley rats were allocated to Control (C), Sedentary diabetic (S), and Exercise diabetic (E) groups (n=15/group). Diabetes was induced via a single intraperitoneal STZ injection (60 mg/kg) and confirmed 72 h post-injection (blood glucose >200 mg/dL). Group E underwent treadmill exercise (30 min/day, 5 days/week, 6 weeks). Blood glucose was assessed longitudinally, and soleus muscle GLUT4, TNF-a, and INSIG1 mRNA expression levels were analyzed post-intervention via qRT-PCR.  Results: Blood glucose levels were 80.33 ± 7.79, 86.33 ± 7.94, and 88.27 ± 6.52 mg/dL at weeks 1, 3, and 6, respectively, in the C group; 356.64 ± 160.63, 361.91 ± 133.09, and 362.64 ± 116.10 mg/dL in the S group; and 452.13 ± 165.34, 376.73 ± 189.70, and 286.80 ± 145.92 mg/dL in the E group. Mixed-effects analysis revealed significant main effects of group (F(2,38) = 29.520, p < 0.001, ηp² = 0.608) and time (F(2,76) = 6.651, p = 0.022, ηp² = 0.149), and a significant group × time interaction (F(4,76) = 9.143, p < 0.001, ηp² = 0.325). Although blood glucose decreased progressively in E, post-test levels did not differ significantly between E and S. GLUT4 mRNA expression was significantly higher, whereas TNF-α mRNA expression was significantly lower in E than S (p < 0.05). No significant difference was observed in INSIG1 mRNA expression between E and S (p > 0.05).  Conclusion: A 6-week high-intensity treadmill exercise regimen was associated with significant GLUT4 upregulation and reduced TNF-α mRNA expression in soleus muscle, without significant post-intervention blood glucose differences compared with sedentary diabetic controls. These findings suggest localized transcriptional adaptations rather than restoration of systemic glucose homeostasis or superior glycemic control under STZ-induced diabetic conditions.
SN  - 1664-2392
ER  -