Tropisetron improves pancreas function and increases insulin synthesis and secretion in the STZ-induced diabetic rats: involvement of UCP2/ZnT8 pathway.
Animals
Blood Glucose
/ drug effects
Diabetes Mellitus, Experimental
/ chemically induced
Diabetes Mellitus, Type 1
/ chemically induced
Glucose Transporter Type 2
/ genetics
Hypoglycemic Agents
/ pharmacology
Insulin
/ biosynthesis
Male
Oxidative Stress
/ drug effects
Pancreas
/ drug effects
Rats, Wistar
Secretory Pathway
Serotonin 5-HT3 Receptor Antagonists
/ pharmacology
Streptozocin
Tropisetron
/ pharmacology
Uncoupling Protein 2
/ metabolism
Zinc Transporter 8
/ metabolism
UCP2
ZnT8
diabetes
insulin
pancreas
tropisetron
Journal
The Journal of pharmacy and pharmacology
ISSN: 2042-7158
Titre abrégé: J Pharm Pharmacol
Pays: England
ID NLM: 0376363
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
02
11
2019
accepted:
21
03
2020
pubmed:
30
4
2020
medline:
14
4
2021
entrez:
30
4
2020
Statut:
ppublish
Résumé
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. 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. 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. This effect might be partly related to the modulated UCP2/ZnT8 signal pathway and improved oxidative stress-induced damage.
Substances chimiques
Blood Glucose
0
Glucose Transporter Type 2
0
Hypoglycemic Agents
0
Insulin
0
Serotonin 5-HT3 Receptor Antagonists
0
Slc2a2 protein, rat
0
Slc30a8 protein, rat
0
Ucp2 protein, rat
0
Uncoupling Protein 2
0
Zinc Transporter 8
0
Streptozocin
5W494URQ81
Tropisetron
6I819NIK1W
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1082-1091Informations de copyright
© 2020 Royal Pharmaceutical Society.
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