Tempol ameliorates STZ-induced T1DM potentially via enhancing AMPK signaling, suppressing pro-apoptotic activity, promoting progenitor cells recruitment, and restoring glucose transporters level

Type 1 diabetes mellitus (T1DM) is a complex metabolic disorder characterized by hyperglycemia, oxidative stress, inflammation, and progressive pancreatic damage. Tempol demonstrated potential antidiabetic effects, however its mechanism of action remains enigmatic. This study hypothesised that tempol improves DM through multiple complementary pathways in experimentally induced T1DM. Thirty male Wistar rats were assigned to control (received intraperitoneal citrate buffer), diabetic (induced by single intraperitoneal injection of streptozotocin (60 mg/kg)), and tempol-treated diabetic (received tempol intraperitoneally at a dose of 100 mg/kg/day for 4 weeks) groups. Tempol significantly reduced fasting blood glucose and improved glucose-insulin homeostasis while increasing serum insulin levels compared with untreated diabetic rats ( p < 0.05), with glucose reduction becoming progressively greater over the treatment period. Tempol also improved liver and kidney functions, attenuated oxidative stress, and reduced inflammatory cytokines ( p < 0.05). Histological and immunohistochemical analyses demonstrated that tempol preserved pancreatic architecture, enhanced insulin and AMPK expression, attenuated pro-apoptotic signaling, and increased CD34 expression ( p < 0.001). In addition, tempol upregulated hepatic and skeletal muscle glucose transporter gene expression ( p < 0.05). These findings indicate that tempol exerts broad antidiabetic effects through multimodal mechanisms beyond its antioxidant nature and represents a promising therapeutic candidate for diabetes management.