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Gemigliptin improves renal function and attenuates podocyte injury in mice with diabetic nephropathy

Cited 32 time in Web of Science Cited 32 time in Scopus
Authors
Jung, Eunsoo; Kim, Junghyun; Kim, Sung Ho; Kim, Sanghwa; Cho, Myung-Haing
Issue Date
2015-08
Citation
European Journal of Pharmacology, Vol.761, pp.116-124
Keywords
ApoptosisDiabetic nephropathyGemigliptinPodocyte
Abstract
Podocytes participate in the formation and regulation of the glomerular filtration barrier. Loss of podocytes occurs during the early stages of diabetic nephropathy and impairs glomerular filtration. Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used as anti-diabetic agents in clinical practice. In this study, we showed that gemigliptin, a novel DPP-4 inhibitor, reduced podocyte apoptosis in type 2 diabetic db/db mice without reducing hyperglycemia. Gemigliptin (100 mg/kg/day) was administered orally for 12 weeks in db/db mice. Blood glucose levels and albuminuria were measured. The renal cortex was collected for histological examination, and molecular assays were used to detect 8-hydroxydeoxyguanosine, advanced oxidation protein products (AOPP), the receptor for advanced glycation end products (RAGE), and integrin-linked kinase (ILK). Type 2 diabetic db/db mice exhibited albuminuria, renal histopathological changes, and podocyte loss. Administration of gemigliptin to db/db mice suppressed albuminuria, enzyme activity and expression of DPP-4, and podocyte apoptosis. The effect of gemigliptin on diabetes-induced podocyte loss was associated with the suppression of oxidative damage, AOPP accumulation, RAGE expression, and ILK expression. These results indicate the possible benefits of using gemigliptin in diabetes patients to treat renal impairment without affecting glycemic control. Copyright (C) 2015 Elsevier B.V. All rights reserved.
ISSN
0014-2999
URI
https://hdl.handle.net/10371/172375
DOI
https://doi.org/10.1016/j.ejphar.2015.04.055
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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