Introduction: Type 1 diabetes (T1D) induces central nervous system complications via impaired hippocampal insulin signaling. The present study investigated the therapeutic potential of endurance training (Ex) and Urtica dioica extract (Ud) on hippocampal insulin pathway markers in diabetic rats.
Materials and Methods: Fifty-six male Wistar rats were divided into eight groups (n=7): healthy control (H-C), H-Ex, H-Ud, H-Ex-Ud, diabetic control (D-C), D-Ex, D-Ud, and D-Ex-Ud. Diabetes was induced by streptozotocin (45 mg/kg). Over 6 weeks, Ex groups underwent moderate treadmill running (5 days/week), while Ud groups received hydroalcoholic extract (50 mg/kg/day orally).
Results: Following diabetes induction, glucose levels significantly increased in diabetic groups. Therapeutic interventions (Ud and Ex) showed positive effects: the D-Ex-Ud group exhibited the fastest glycemic improvement by the second week (p=0.02), with sustained blood glucose reduction until the final week. Western blot analyses revealed decreased insulin and GLUT4 proteins in the diabetic hippocampus. Monotherapies (Ud and Ex) increased insulin expression (p=0.03) and GLUT4 (p=0.001), respectively, while the combined therapy (D-Ex-Ud) simultaneously and synergistically improved both markers (p=0.001).
Conclusion: Six weeks of endurance training and Urtica dioica extract improve glycemic control and restore hippocampal insulin/GLUT4 expression in T1D rats, with combined intervention yielding superior outcomes. This dual approach represents a promising non-pharmacological strategy for mitigating diabetic neuropathology.