Background & Aims: Diabetes mellitus is a long-term metabolic disorder that arises from insufficient insulin production, reduced insulin activity, or both, resulting in chronic hyperglycemia and widespread metabolic disturbances. It affects how the body processes carbohydrates, fats, and proteins, leading over time to damage in organs such as the liver, kidneys, and blood vessels. The liver, as one of the principal organs involved in maintaining blood glucose homeostasis, plays a fundamental role through glycogen storage, gluconeogenesis, and various enzymatic pathways that regulate glucose and insulin dynamics. When diabetes develops, the liver’s ability to respond to insulin becomes compromised, disrupting glucose turnover, lipid metabolism, and overall energy balance. Therefore, understanding how different interventions influence hepatic metabolic function and insulin levels in diabetes is essential for developing new therapeutic strategies. Exercise has long been recognized as a cornerstone of diabetes management due to its broad effects on glucose regulation and metabolic adaptation. Endurance training, commonly defined as prolonged, moderate-intensity aerobic activity such as treadmill running, is known to increase insulin sensitivity, improve mitochondrial efficiency, and stimulate glucose uptake into skeletal muscle. These adaptations collectively help reduce hyperglycemia and improve systemic insulin utilization. In addition to muscle tissue, regular aerobic exercise exerts effects on the liver by enhancing oxidative metabolism, limiting lipid accumulation, and modulating key pathways involved in gluconeogenesis and glycogen synthesis. Through these mechanisms, endurance exercise contributes not only to better glucose handling but also to improved hepatic function in diabetic conditions. This study aimed to investigate the effect of eight weeks of endurance training combined with nettle extract supplementation on insulin levels in the liver tissue of diabetic male rats. Methods: In this experimental study, 48 healthy male rats were purchased and, after adaptation, divided into 6 groups (Healthy Control, Endurance Training, Diabetic Control, Diabetes + Nettle, Diabetes + Aerobic, and Diabetes + Aerobic + Nettle), with 8 rats per group. Diabetes was induced by an intraperitoneal injection of STZ (50 mg/kg) and confirmed by blood glucose measurement. The eight-week aerobic training protocol was performed on a treadmill, and nettle extract (150 mg/kg) was administered via gavage five days a week. At the end of the period, hepatic insulin levels were analyzed. Results: The findings indicated that after eight weeks of intervention, a statistically significant difference was observed in hepatic insulin levels among the studied groups. Specifically, groups undergoing endurance training and/or nettle extract consumption showed different tissue insulin levels compared to the diabetic control group, suggesting the impact of these interventions on insulin metabolism in the liver. Conclusion: Diabetes is a chronic metabolic disorder characterized primarily by persistent hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Over time, this imbalance disrupts normal carbohydrate, fat, and protein metabolism and contributes to the development of various complications affecting multiple organs, including the liver. The liver plays a crucial role in glucose homeostasis through processes such as glycogen storage, gluconeogenesis, and regulation of insulin signaling. In diabetic conditions, hepatic metabolism becomes dysregulated, leading to impaired insulin sensitivity and altered insulin handling within liver tissue. Consequently, identifying strategies that can improve hepatic metabolic function and insulin regulation has become an important focus in diabetes research. Among the non‑pharmacological approaches that have received increasing attention are physical activity and the use of plant‑derived bioactive compounds. Endurance exercise is widely recognized as an effective strategy for improving metabolic health. Regular aerobic training enhances glucose uptake, increases insulin sensitivity, and improves mitochondrial efficiency in several tissues. Exercise also influences hepatic metabolism by improving lipid oxidation, reducing oxidative stress, and modulating pathways related to glucose production and insulin signaling. Through these mechanisms, endurance training may help counteract some of the metabolic disturbances associated with diabetes. In addition to exercise, medicinal plants and their extracts have been investigated for their potential therapeutic effects in metabolic disorders. Nettle (Urtica dioica) is one such plant that has been used in traditional medicine for centuries. It contains a variety of bioactive compounds, including flavonoids, phenolic acids, vitamins, and minerals, many of which possess antioxidant, anti‑inflammatory, and metabolic regulatory properties. Previous studies suggest that nettle extract may contribute to improved glucose metabolism by enhancing insulin secretion, protecting pancreatic beta cells, and reducing oxidative stress. These properties make nettle a promising natural supplement for supporting metabolic health in diabetic conditions. Combining exercise interventions with plant‑based supplementation may provide synergistic benefits. While endurance training improves metabolic efficiency and insulin sensitivity through physiological adaptations, nettle extract may exert complementary biochemical effects by modulating oxidative balance and metabolic signaling pathways. Investigating the combined impact of these two interventions may therefore provide valuable insights into integrated strategies for improving metabolic regulation in diabetes. Experimental animal models are commonly used to study diabetes and evaluate potential therapeutic interventions. Streptozotocin‑induced diabetes in laboratory rats is widely utilized because it mimics several metabolic characteristics observed in human diabetes. Streptozotocin selectively damages pancreatic beta cells, leading to reduced insulin production and elevated blood glucose levels. This model allows researchers to examine how different treatments influence metabolic markers such as insulin levels within specific tissues, including the liver. Evidence from experimental investigations suggests that interventions involving regular aerobic exercise or herbal supplementation can alter metabolic responses in diabetic organisms. When applied together, these strategies may enhance adaptive responses related to glucose metabolism, oxidative balance, and hormonal regulation. Such findings support the idea that integrated lifestyle and nutritional approaches may hold promise for improving metabolic outcomes in diabetes. examining the interaction between physical training and plant‑based supplementation provides a meaningful framework for understanding alternative or complementary strategies in metabolic disease management. Insights gained from controlled experimental studies in animal models can contribute to a deeper understanding of underlying mechanisms and may guide future research aimed at translating these findings into clinical contexts. Continued investigation is necessary to determine the precise pathways through which exercise and botanical compounds influence hepatic metabolism and insulin regulation. |