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

• Published in: Mediators of Inflammation Vol. 2014; no. 5; pp. 329 - 343
• Main Authors: Fernandes, Rosa, Reis, Flávio, Teixeira, Frederico, Teixeira de Lemos, Edite, Rodrigues-Santos, Paulo, Gonçalves, Andreia, Mega, Cristina, Marques, Catarina, Fontes-Ribeiro, Carlos
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Limiteds 01.01.2014; Hindawi Publishing Corporation; Hindawi Limited
• Subjects: Animals; Apoptosis - drug effects; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; Glucagon-Like Peptide 1 - metabolism; Inflammation - metabolism; Inflammation - prevention & control; Kidney - drug effects; Kidney - metabolism; Pyrazines - therapeutic use; Rats; Rats, Zucker; Sitagliptin Phosphate; Triazoles - therapeutic use; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2014/538737

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 HbA 1c 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-1 β , 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 HbA 1c (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 β 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.