Nilotinib enhances β-islets integrity and secretory functions in a rat model of STZ-induced diabetes mellitus.

Type 1 diabetes mellitus (DM) remains an intractable disease with a limited number of therapeutic options. Recently, some studies have reported the role of inflammation in DM-induced β-cell destruction. Nilotinib hydrochloride, a tyrosine kinase inhibitor is a well-known anticancer with numerous medical benefits. In the present study, DM was induced by single I.P. injection of streptozotocin (STZ) (50 mg/kg). Daily oral nilotinib (10 mg/kg) and (20 mg/kg) for 4 weeks induced a significant attenuation of DM signs in rats and their assessed lab values. Nilotinib induced a dose-dependent significant escalation in serum insulin level with a significant reduction in blood glucose and glucagon levels. Nevertheless, biomarkers of cell injury, tissue necrosis, and apoptosis; caspase-3 were significantly reduced. Moreover, pancreatic antioxidants defenses of which; thioredoxin, superoxide dismutase (SOD) and catalase activities, reduced glutathione (GSH) concentration, and total antioxidant capacity significantly improved with a simultaneous reduction in malondialdehyde (MDA) content. Histopathologically, nilotinib treatment was associated with a minimal pancreatic injury with a significant restoration of insulin content in β-islets. In addition, nilotinib treatment revealed a significant reduction in infiltration of macrophages in β-cells. In conclusion: nilotinib's ameliorative impact on DM may be attributed to both nilotinib's mediated protection and preservation of pancreatic β islets function and the improvement in serum insulin levels and hence the improvement of blood glucose.