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Experimental Diabetes Research
Volume 2011, Article ID 162092, 12 pages
Research Article

Diabetic Nephropathy Amelioration by a Low-Dose Sitagliptin in an Animal Model of Type 2 Diabetes (Zucker Diabetic Fatty Rat)

1Laboratory of Pharmacology & Experimental Therapeutics, Institute for Biomedical Research on Light and Image (IBILI), Medicine Faculty, Coimbra University, 3000-548 Coimbra, Portugal
2Agrarian School of Viseu, Polytechnic Institute of Viseu, 3500-606 Viseu, Portugal
3Educational, Technologies and Health Study Center, Polytechnic Institute of Viseu, 3504-510 Viseu, Portugal

Received 1 July 2011; Revised 21 August 2011; Accepted 29 August 2011

Academic Editor: Yoshio Shimizu

Copyright © 2011 Cristina Mega 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.


This study was performed to assess the effect of chronic low-dose sitagliptin, a dipeptidyl peptidase 4 inhibitor, on metabolic profile and on renal lesions aggravation in a rat model of type-2 diabetic nephropathy, the Zucker diabetic fatty (ZDF) rat. Diabetic and obese ZDF (fa/fa) rats and their controls ZDF (+/+) were treated for 6 weeks with vehicle (control) or sitagliptin (10 mg/kg/bw). Blood/serum glucose, HbA1c, insulin, Total-c, TGs, urea, and creatinine were assessed, as well as kidney glomerular and tubulointerstitial lesions (interstitial fibrosis/tubular atrophy), using a semiquantitative rating from 0 (absent/normal) to 3 (severe and extensive damage). Vascular lesions were scored from 0–2. Sitagliptin in the diabetic rats promoted an amelioration of glycemia, HbA1c, Total-c, and TGs, accompanied by a partial prevention of insulinopenia. Furthermore, together with urea increment prevention, renal lesions were ameliorated in the diabetic rats, including glomerular, tubulointerstitial, and vascular lesions, accompanied by reduced lipid peroxidation. In conclusion, chronic low-dose sitagliptin treatment was able to ameliorate diabetic nephropathy, which might represent a key step forward in the management of T2DM and this serious complication.