Tropisetron attenuates pancreas apoptosis in the STZ-induced diabetic rats: involvement of SIRT1/NF-κB signaling.
BACKGROUND
Diabetes mellitus (DM) is one of the most common diseases in the worldwide. Type 1 diabetes mellitus (T1DM) is characterized by insulin deficiency and beta cells apoptosis. Tropisetron as a 5-HT3 receptor antagonist has positive effects on the inflammation, apoptosis and glucose lowering. The aim of this study was to investigate the effect of tropisetron on β-cells apoptosis and its possible pathways.


METHODS
Animals were divided into five equal groups: the control, tropisetron, diabetes, tropisetron-DM and glibenclamide-DM (seven in each group). Tropisetron and glibenclamide were administrated for 2 weeks after type 1 diabetes induction. Real-time PCR, western blot analysis and TUNEL assay were performed.


RESULTS
We found that tropisetron decreased blood glucose and increased insulin secretion. Protein expression of NF-κB was downregulated, while protein expression of SIRT1 upregulated after tropisetron treatment. Moreover, Bax/Bcl2 ratio decreased in tropisetron-DM group and finally, apoptosis improved in pancreas tissue.


CONCLUSIONS
It seems that tropisetron administration improves STZ-induced apoptosis and diabetes in the animals. This effect might be resulted from involvement in NF-κB/ SIRT1 pathway.
['Naderi|Roya|R|', 'Shirpoor|Alireza|A|', 'Samadi|Mahrokh|M|', 'Pourheydar|Bagher|B|', 'Moslehi|Azam|A|http://orcid.org/0000-0003-1153-1475']
D000818:Animals D017209:Apoptosis D003921:Diabetes Mellitus, Experimental D003922:Diabetes Mellitus, Type 1 D008297:Male D016328:NF-kappa B D010179:Pancreas D019253:Proto-Oncogene Proteins c-bcl-2 D051381:Rats D017208:Rats, Wistar D058831:Serotonin 5-HT3 Receptor Antagonists D015398:Signal Transduction D056564:Sirtuin 1 D013311:Streptozocin D000077526:Tropisetron
Tropisetron Pancreas Diabetes SIRT1 NF-κb Insulin