CB-1R and GLP-1R gene expressions and oxidative stress in the liver of diabetic rats treated with sitagliptin

Background type 2 diabetes is a major health problem affecting millions of people. controlled eating and regular physical activity are important for the management of type 2 diabetes. dipeptidyl peptidase-4 enzyme (dpp-4) inhibitor sitagliptin is a potent agent for the treatment of type-2 diabetes. the aim of this study was to examine the effects of sitagliptin on the liver of rats with streptozotocin (stz)-induced diabetes,in terms of (i) the expression levels of the cannabinoid 1 receptor (cb-1r) and glucagon-like peptide 1 receptor (glp-1r),(ii) alterations in the number and localization of these peptides,and (iii) changes in histological and oxidative damage. methods thirty-two neonatal (two-day-old) rats,which were divided into four groups,were treated with saline (control),sitagliptin (control; 1.5 mg/kg/day for 15 days starting from day 5 of the experimental period),stz (diabetes; 100 mg/kg single dose),stz + sitagliptin (diabetes + sitagliptin). after 20 days,hepatic tissues were obtained from rats. results the expressions of glp-1r and cb-1r mrna increased approximately 1.89- and 2.94-fold,respectively,in the diabetes + sitagliptin group as compared to the diabetic group. additionally the number of glp-1r immunopositive cells decreased and cb-1r immunopositive cells increased in comparison to the diabetic group; however,this was not statistically significant. glutathione levels increased,but malondialdehyde and protein carbonyl levels decreased in the diabetes + sitagliptin group more than the diabetic group. conclusion our findings indicate that sitagliptin treatment regulates glp-1r and cb-1r gene expressions,which are associated with appetite regulation in diabetic rat,and may decrease oxidative stress and liver tissue damage. © 2017 institute of pharmacology,polish academy of sciences