An Evaluation of the Effects of the Ruthenium (II)–Uracil Schiff Base Complex on Selected Markers of Glucose Homeostasis in Diet-Induced Prediabetic Male Rats

Background: The onset of type 2 diabetes mellitus (T2DM) is often preceded by prediabetes, a reversible state of insulin resistance and impaired glucose regulation driven by the chronic consumption of a high-calorie diet and sedentary lifestyle. Prediabetes is characterised by impaired glucose tolerance and elevated glycated haemoglobin (HbA1c). Although metformin improves insulin sensitivity, adherence limitations to lifestyle interventions highlight the need for alternative drugs that can be effective even without dietary intervention. In our laboratory, we synthesised a novel ruthenium complex that exhibits elevated biological activity. Accordingly, this study investigated the metabolic effects of a novel ruthenium (II)–uracil Schiff base complex in HFHC diet-induced prediabetic rats, with and without dietary intervention. Methods: Forty-eight male Sprague-Dawley rats (150–180 g) were divided into two groups, the standard diet (n = 12) and HFHC diet groups (n = 36), for prediabetic induction. Prediabetic animals were randomly assigned to respective treatment groups. The ruthenium complex was administered to prediabetic rats once a day, every third day, for 12 weeks, while monitoring changes in blood glucose, caloric intake, and body weight. Results: Diet-induced prediabetes resulted in increased fasting blood glucose and elevated HbA1c. The administration of the ruthenium (II)–uracil Schiff base complex reduced fasting blood glucose, improved insulin levels and ghrelin, enhanced GLUT4 expression, and significantly increased skeletal muscle glycogen, especially when combined with dietary intervention. Conclusions: The findings showed that the ruthenium complex exerts a pronounced effect on ameliorating glucose homeostasis, enhancing skeletal muscle glucose uptake, and improving overall metabolic function.