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

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.