Roya Naderi1,2, Alireza Shirpoor1,2, Mahrokh Samadi3, Bagher Pourheydar4,5, Azam Moslehi6. 1. Nephrology and Kidney Transplant Research Center, Urmia University of Medical Sciences, Urmia, Iran. 2. Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran. 3. Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran. 4. Neurophysiology Research Center, Urmia University of Medical Sciences, Urmia, Iran. 5. Department of Anatomical Sciences, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran. 6. Cellular & Molecular Research Center, Qom University of Medical Sciences, Qom, Iran.
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.
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 diabeticrats 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 diabeticrats. 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.