Modulating insulin secretion and inflammation against sodium arsenite toxicity by levosimendan as a novel pancreatic islets' protector

Levosimendan (LEVO) is a calcium sensitizer with established inotropic and vasodilator impacts associated with ATP-sensitive potassium channels (K-ATP). Although LEVO's role in modulating oxidative stress of cardiac cells has been studied, in the current study, LEVO was used, for the first time, to investigate its preventive and therapeutic roles in pancreatic islets through viability, functionality, and inflammation pathways as well as oxidative stress against the toxicity induced by sodium arsenite (NaAsO2). Following the optimization studies to select the proper concentrations of LEVO and NaAsO2, isolated pancreatic islets were exposed to different combinations of NaAsO2 and LEVO. MTT assay, glucose-dependent insulin secretion test, investigation of oxidative stress and inflammation biomarkers in addition to qualification of the expressions of P16, P38, and NF-kappa B genes were performed to assess different underlying mechanisms to investigate the protective role of LEVO against NaAsO2-induced toxicity. This study demonstrated that NaAsO2-treated pancreatic islets' exposure to LEVO improved their viability and functionality while modulating the generation of oxidative stress and inflammatory biomarkers. Therefore LEVO caused significant recoveries in the characteristics of the islets. The main conclusion is that LEVO showed protective impacts in pancreatic islets against exposure to NaAsO2. However, therapeutic uses of LEVO in the field of diabetes need further investigations.

Automated summary

In this study, the protective effects of Levosimendan (LEVO) on pancreatic islets exposed to sodium arsenite (NaAsO2) were investigated. The results showed that LEVO improved the viability and functionality of pancreatic islets and modulated oxidative stress and inflammatory biomarkers.