Rushikesh Kale *
Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The disease has reached epidemic proportions globally, affecting an estimated 537 million adults worldwide, a number projected to rise to 643 million by 2030 according to the International Diabetes Federation (IDF) [1]. The pathophysiology of diabetes mellitus involves disturbances in carbohydrate, lipid, and protein metabolism, often accompanied by oxidative stress, chronic inflammation, and endothelial dysfunction [2]. Chronic hyperglycemia leads to severe complications such as nephropathy, neuropathy, retinopathy, and cardiovascular diseases, significantly increasing morbidity and mortality rates among affected individuals [3]. Despite the availability of several pharmacological interventions including insulin, sulfonylureas, biguanides, thiazolidinediones, and DPP-4 inhibitors, the effective management of diabetes remains a major challenge. Many of these agents exhibit limited efficacy over time and are associated with undesirable side effects such as hypoglycemia, weight gain, and gastrointestinal disturbances [4,5]. Consequently, there is a continuous need to explore new therapeutic strategies, including the repurposing of existing drugs with favorable safety profiles for novel indications [6]. Experimental animal models play a pivotal role in diabetes research by providing valuable insights into disease mechanisms and facilitating the evaluation of potential antidiabetic agents before clinical translation. Among these, rodent models are most widely used due to their physiological similarity to humans, reproducibility, and well-characterized metabolic pathways [7]. Atovaquone, a hydroxy-naphthoquinone derivative primarily used as an antimalarial and antipneumocystis agent, has recently garnered attention for its pleiotropic pharmacological properties beyond antiparasitic activity [8]. It exhibits potent antioxidant, anti-inflammatory, and mitochondrial modulatory effects, which may contribute to its potential antidiabetic efficacy [9]. Given the involvement of oxidative stress and mitochondrial dysfunction in diabetes pathogenesis, exploring Atovaquone’s effect on glucose metabolism and pancreatic β-cell protection in experimental diabetic models is scientifically justified. Therefore, investigating the antidiabetic potential of Atovaquone against streptozotocin (STZ)-induced diabetic rats may provide novel insights into drug repurposing for metabolic disorders [10].
10.5281/zenodo.18472891