Subject    :    [2016 Jun;40(3)] Renoprotective Effect of Gemigliptin, a Dipeptidyl Peptidase-4 Inhibitor, in Streptozotocin-Induced Type 1 Diabetic Mice
Writer KDA
Date 2016-07-05 17:14:37 Hit 6,048
LINK URL http://e-dmj.org/DOIx.php?id=10.4093/dmj.2016.40.3.211 (Click 401)

 
Diabetes Metab J. 2016 Jun;40(3):211-221. English.
Published online Mar 31, 2016.  http://dx.doi.org/10.4093/dmj.2016.40.3.211 
Copyright © 2016 Korean Diabetes Association
   
Renoprotective Effect of Gemigliptin, a Dipeptidyl Peptidase-4 Inhibitor, in Streptozotocin-Induced Type 1 Diabetic Mice
Gwon-Soo Jung,1 Jae-Han Jeon,1 Mi Sun Choe,2 Sung-Woo Kim,1 In-Kyu Lee,1 Mi-Kyung Kim,3,* andKeun-Gyu Park1,*
1Division of Endocrinology and Metabolism, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
2Department of Pathology, Keimyung University School of Medicine, Daegu, Korea.
3Division of Endocrinology and Metabolism, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea.

Corresponding author: Keun-Gyu Park. Division of Endocrinology and Metabolism, Department of Internal Medicine, Kyungpook National University School of Medicine, 130 Dongdeok-ro, Jung-gu, Daegu 41944, Korea. Email: kpark@knu.ac.kr Corresponding author: Mi-Kyung Kim. Division of Endocrinology and Metabolism, Department of Internal Medicine, Keimyung University School of Medicine, 56 Dalseong-ro, Jung-gu, Daegu 41931, Korea. Email: mdkmk@dsmc.or.kr

 

*Gwon-Soo Jung and Jae-Han Jeon contributed equally to this study as first authors.
 
Received July 13, 2015; Accepted September 22, 2015.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

 
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 I collagen and fibronectin, and Smad3 phosphorylation. In cultured rat renal cells, gemigliptin inhibited transforming growth factor β-stimulated type I 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.

   
Keywords:
Diabetes mellitus, type 1; DPP-4 inhibitor; Renal fibrosis
 

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