Sitagliptin prevents inflammation and apoptotic cell death in the kidney of type 2 diabetic animals.

Abstract

This study aimed to evaluate the efficacy of sitagliptin, a dipeptidyl peptidase IV (DPP-IV) inhibitor, in preventing the deleterious effects of diabetes on the kidney in an animal model of type 2 diabetes mellitus; the Zucker diabetic fatty (ZDF) rat: 20-week-old rats were treated with sitagliptin (10 mg/kg bw/day) during 6 weeks. Glycaemia and blood HbA1c levels were monitored, as well as kidney function and lesions. Kidney mRNA and/or protein content/distribution of DPP-IV, GLP-1, GLP-1R, TNF-α, IL-1β, BAX, Bcl-2, and Bid were evaluated by RT-PCR and/or western blotting/immunohistochemistry. Sitagliptin treatment improved glycaemic control, as reflected by the significantly reduced levels of glycaemia and HbA1c (by about 22.5% and 1.2%, resp.) and ameliorated tubulointerstitial and glomerular lesions. Sitagliptin prevented the diabetes-induced increase in DPP-IV levels and the decrease in GLP-1 levels in kidney. Sitagliptin increased colocalization of GLP-1 and GLP-1R in the diabetic kidney. Sitagliptin also decreased IL-1β and TNF-α levels, as well as, prevented the increase of BAX/Bcl-2 ratio, Bid protein levels, and TUNEL-positive cells which indicates protective effects against inflammation and proapoptotic state in the kidney of diabetic rats, respectively. In conclusion, sitagliptin might have a major role in preventing diabetic nephropathy evolution due to anti-inflammatory and antiapoptotic properties.

• Authors: Catarina Marques, Cristina Mega, Andreia Gonçalves, Paulo Rodrigues-Santos, Edite Teixeira-Lemos, Frederico Teixeira, Carlos Fontes-Ribeiro, Flávio Reis, Rosa Fernandes
• Journal: Mediators of inflammation (Mediators Inflamm) Vol. 2014 Pg. 538737 ( 2014) ISSN: 1466-1861 [Electronic] United States
• PMID: 24817793 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dipeptidyl-Peptidase IV Inhibitors
• Pyrazines
• Triazoles
• Tumor Necrosis Factor-alpha
• Glucagon-Like Peptide 1
• Sitagliptin Phosphate

Topics

• Animals
• Apoptosis (drug effects)
• Diabetes Mellitus, Experimental (drug therapy, metabolism)
• Diabetes Mellitus, Type 2 (drug therapy, metabolism)
• Dipeptidyl-Peptidase IV Inhibitors (therapeutic use)
• Glucagon-Like Peptide 1 (metabolism)
• Inflammation (metabolism, prevention & control)
• Kidney (drug effects, metabolism)
• Pyrazines (therapeutic use)
• Rats
• Rats, Zucker
• Sitagliptin Phosphate
• Triazoles (therapeutic use)
• Tumor Necrosis Factor-alpha (metabolism)