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

Abstract

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.

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Correspondence to Sema Bolkent.

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Coskun, Z.M., Koyuturk, M., Karabulut, S. et al. CB-1R and GLP-1R gene expressions and oxidative stress in the liver of diabetic rats treated with sitagliptin. Pharmacol. Rep 69, 822–829 (2017). https://doi.org/10.1016/j.pharep.2017.03.013

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  • DOI: https://doi.org/10.1016/j.pharep.2017.03.013

Keywords

  • Sitagliptin
  • Diabetes
  • Cannabinoid 1 receptor
  • Glucagon like peptide 1 receptor
  • Oxidative stress