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

Abstract

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. Thirty-two neonatal (two-day-old) rats, which were divided into four groups, were treated with saline (control), sitagliptin (control; 1.5mg/kg/day for 15 days starting from day 5 of the experimental period), STZ (diabetes; 100mg/kg single dose), STZ+sitagliptin (diabetes+sitagliptin). After 20 days, hepatic tissues were obtained from rats. 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. 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.