Tropisetron improves pancreas function and increases insulin synthesis and secretion in the STZ-induced diabetic rats: involvement of UCP2/ZnT8 pathway

Abstract

Abstract Objectives Diabetes mellitus is one of the most common metabolic diseases. Tropisetron, as a 5-HT3 receptor antagonist, has a considerable role in the inflammation and oxidative stress lowering. This study aimed to investigate the effect of this 5-HT3 receptor antagonist on insulin secretion in male diabetic rats and the possible mechanisms. Methods Animals were divided into five equal groups; the control, tropisetron, diabetes, tropisetron–diabetes and glibenclamide–diabetes (7 in each group). Tropisetron and glibenclamide were administrated for 2 weeks after inducing type 1 diabetes. Key findings We demonstrated that insulin secretion improved robustly in diabetes–tropisetron compared with the diabetic group. Oxidative stress biomarkers were lower in a diabetes–tropisetron group than in diabetic rats. Simultaneously, tropisetron administration promoted the expression of ZnT8 and GLUT2 and also beta-cell mass in pancreatic tissue, while the expression of uncoupling protein 2 (UCP2) was restrained. The histological evaluation confirmed our results. These effects were equipotent with glibenclamide, indicating that tropisetron can protect islets from the abnormal insulin secretion and morphological changes induced by type 1 diabetes. Conclusions This effect might be partly related to the modulated UCP2/ZnT8 signal pathway and improved oxidative stress-induced damage.