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

Abstract EN

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.