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Renoprotective Effect of Gemigliptin, a Dipeptidyl Peptidase-4 Inhibitor, in Streptozotocin-Induced Type 1 Diabetic Mice

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Author(s)
Gwon-Soo JungJae-Han JeonMi Sun ChoeSung-Woo KimIn-Kyu LeeMi-Kyung KimKeun-Gyu Park
Keimyung Author(s)
Choe, Mi SunKim, Mi Kyung
Department
Dept. of Pathology (병리학)
Dept. of Internal Medicine (내과학)
Journal Title
Diabetes & Metabolism Journal
Issued Date
2016
Volume
40
Issue
3
Keyword
Diabetes mellitus, type 1DPP-4 inhibitorRenal fibrosis
Abstract
Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used in the treatment of patients with type 2 diabetes and
have proven protective effects on diabetic kidney disease (DKD). Whether DPP-4 inhibitors have renoprotective effects on insulin-
deficient type 1 diabetes has not been comprehensively examined. The aim of this study was to determine whether gemigliptin,
a new DPP-4 inhibitor, has renoprotective effects in streptozotocin (STZ)-induced type 1 diabetic mice.
Methods: Diabetes was induced by intraperitoneal administration of a single dose of STZ. Mice with diabetes were treated without
or with gemigliptin (300 mg/kg) for 8 weeks. Morphological changes of the glomerular basement membrane (GBM) were
observed by electron microscopy and periodic-acid Schiff staining. In addition, we measured blood glucose and urinary albumin
excretion and evaluated fibrotic markers using immunohistochemical staining, quantitative reverse transcription polymerase
chain reaction analysis, and Western blot analysis.
Results: Gemigliptin did not reduce the blood glucose levels of STZ-treated mice. In gemigliptin-treated mice with STZ, a significant
reduction in urinary albumin excretion and GBM thickness was observed. Immunohistological examination revealed
that gemigliptin attenuated renal fibrosis induced by STZ and decreased extracellular matrix protein levels, including those of
type Ι collagen and fibronectin, and Smad3 phosphorylation. In cultured rat renal cells, gemigliptin inhibited transforming
growth factor β-stimulated type Ι collagen and fibronectin mRNA and protein levels via down-regulation of Smad3 phosphorylation.
Conclusion: Our data demonstrate that gemigliptin has renoprotective effects on DKD, regardless of its glucose-lowering effect,
suggesting that it could be used to prevent DKD, including in patients with type 1 diabetes.
Keimyung Author(s)(Kor)
최미선
김미경
Publisher
School of Medicine
Citation
Gwon-Soo Jung et al. (2016). Renoprotective Effect of Gemigliptin, a Dipeptidyl Peptidase-4 Inhibitor, in Streptozotocin-Induced Type 1 Diabetic Mice. Diabetes & Metabolism Journal, 40(3), 211–221. doi: 10.4093/dmj.2016.40.3.211
Type
Article
ISSN
2233-6079
DOI
10.4093/dmj.2016.40.3.211
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33280
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
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