Biochemical and molecular effects of atorvastatin and rosuvastatin on insulin sensitivity in rats

Objective: To evaluate the effects of atorvastatin and rosuvastatin on glucose regulation and insulin sensitivity in rats, focusing on biochemical, histological, and molecular changes. Methods: Thirty male albino rats were randomised into three groups (n=10 each): control, atorvastatin (80 mg/kg), and rosuvastatin (40 mg/kg). Treatments were given orally for 30 days. Serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), oral glucose tolerance test (OGTT), and fasting blood glucose (FBG) were measured. Pancreatic tissue was examined histologically. The molecular signalling pathway was studied by measuring the gene expression of protein kinase B (AKT) and Insulin-responsive glucose transporter type 4 (GLUT4) in adipose tissue and skeletal muscle. Results: [Atorvastatin treatment was associated with an initial reduction in fasting blood glucose and improvement in insulin sensitivity. However, by day 30, this group showed reduced glucose tolerance, increased insulin resistance, and β-cell alterations. These metabolic changes were accompanied by a transient early upregulation of AKT and GLUT4 expression in adipose tissue, which declined by the end of the study. In contrast, rosuvastatin treatment was associated with early improvement in glycaemic markers and preserved glucose tolerance, with histological changes observed in pancreatic tissue. Molecular analysis in this group showed a modest early upregulation of AKT and GLUT4 in skeletal muscle. Conclusion: Atorvastatin and rosuvastatin exert distinct effects on glucose metabolism. While rosuvastatin showed a more stable metabolic profile, prolonged high-dose atorvastatin was associated with insulin resistance and β-cell changes.