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Mediators of Inflammation
Volume 2014, Article ID 538737, 15 pages
http://dx.doi.org/10.1155/2014/538737
Research Article

Sitagliptin Prevents Inflammation and Apoptotic Cell Death in the Kidney of Type 2 Diabetic Animals

1Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal
2ESAV, Technologies and Health Study Center, Polytechnic Institute of Viseu, 3504-510 Viseu, Portugal
3Educational Technologies and Health Study Center, Polytechnic Institute of Viseu, 3504-510 Viseu, Portugal
4Institute of Immunology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
5Immunology and Oncology Laboratory, CNC, 3004-517 Coimbra, Portugal
6Center of Ophthalmology and Vision Sciences, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal

Received 10 January 2014; Revised 6 March 2014; Accepted 6 March 2014; Published 8 April 2014

Academic Editor: Fulvio D’Acquisto

Copyright © 2014 Catarina Marques et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 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-, IL-1, 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 (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-1 and TNF- 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.