Modulatory role of imatinib mesylate on pancreatic β-cells' secretory functions in an STZ rat model of diabetes mellitus

The present study was undertaken to assess the effect of imatinib mesylate; a tyrosine kinase inhibitor and a wellknown anticancer with numerous medical benefits on blood sugar levels, insulin, and glucagon secretion in an experimental model of STZ-induced diabetes mellitus. Type 1 diabetes mellitus (T1DM) was induced by a single I. P. injection of Streptozotocin (STZ) (50 mg/kg) in male Sprague-Dawley rats. Daily oral imatinib (10 mg/kg) and (20 mg/kg) for 4 weeks induced a significant attenuation in signs of DM in rats reflected in their assessed lab values. Biomarkers of cell injury, tissue necrosis, and apoptosis; caspase-3 were significantly reduced with imatinib treatment. Furthermore, pancreatic antioxidants defenses of which; superoxide dismutase (SOD) and catalase activities, reduced glutathione (GSH) concentration, and total antioxidant capacity have significantly improved with a simultaneous reduction in malondialdehyde (MDA) content. Histopathologically, imatinib treatment was associated with a minimal pancreatic injury and marked restoration of insulin content in beta-cells. Moreover, imatinib treatment revealed a significant reduction in the infiltration of macrophages in beta-cells. Imatinib's ameliorative impact on DM may be attributed to it's mediated protection and preservation of pancreatic beta-cells function and the improvement in serum insulin levels and hence the improvement of blood glucose and overall glycemic control.