Browse

Dipeptidyl peptidase IV inhibitor attenuates kidney injury in rat remnant kidney

Cited 49 time in Web of Science Cited 50 time in Scopus
Authors
Joo, Kwon Wook; Kim, Sejoong; Ahn, Shin-young; Chin, Ho Jun; Chae, Dong-Wan; Lee, Jeonghwan; Han, Jin Suk; Na, Ki Young
Issue Date
2013-04-27
Publisher
BioMed Central
Citation
BMC Nephrology, vol.14 no.98
Keywords
Dipeptidyl peptidase IVGlucagon-like peptide-1 receptorFoxO3aSitagliptinKidney injury
Abstract
Background : The inhibition of dipeptidyl peptidase (DPP) IV shows protective effects on tissue injury of the heart, lung, and kidney. Forkhead box O (FoxO) transcriptional factors regulate cellular differentiation, growth, survival, the cell cycle, metabolism, and oxidative stress. The aims of this study were to investigate whether the DPP IV inhibitor sitagliptin could attenuate kidney injury and to evaluate the status of FoxO3a signaling in the rat remnant kidney model.

Methods : Rats were received two-step surgery of 5/6 renal mass reduction and fed on an oral dose of 200 mg/kg/day sitagliptin for 8 weeks. Before and after the administration of sitagliptin, physiologic parameters were measured. After 8 weeks of treatment, the kidneys were harvested.
Results : The sitagliptin treatment attenuated renal dysfunction. A histological evaluation revealed that glomerulosclerosis and tubulointerstitial injury were significantly decreased by sitagliptin. Sitagliptin decreased DPP IV activity and increased the renal expression of glucagon-like peptide-1 receptor (GLP-1R). The subtotal nephrectomy led to the activation of phosphatidylinositol 3-kinase (PI3K)-Akt and FoxO3a phosphorylation, whereas sitagliptin treatment reversed these changes, resulting in PI3K-Akt pathway inactivation and FoxO3a dephosphorylation. The renal expression of catalase was increased and the phosphorylation of c-Jun N-terminal kinase (JNK) was decreased by sitagliptin. Sitagliptin treatment reduced apoptosis by decreasing cleaved caspase-3 and −9 and Bax levels and decreased macrophage infiltration.

Conclusions : In rat remnant kidneys, DPP IV inhibitor attenuated renal dysfunction and structural damage. A reduction of apoptosis, inflammation and an increase of antioxidant could be suggested as a renoprotective mechanism together with the activation of FoxO3a signaling. Therefore, DPP IV inhibitors might provide a promising approach for treating CKD, but their application in clinical practice remains to be investigated.
ISSN
1471-2369
Language
English
URI
http://www.biomedcentral.com/1471-2369/14/98

http://hdl.handle.net/10371/82535
DOI
https://doi.org/10.1186/1471-2369-14-98
Files in This Item:
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Journal Papers (저널논문_의학과)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse