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Horm Metab Res 2014; 46(10): 717-721
DOI: 10.1055/s-0034-1371892
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Linagliptin Blocks Renal Damage in Type 1 Diabetic Rats by Suppressing Advanced Glycation End Products-Receptor Axis

S. Nakashima
1   Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan
,
T. Matsui
1   Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan
,
M. Takeuchi
2   Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Kanazawa, Japan
,
S.-I. Yamagishi
1   Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan
› Author Affiliations
Further Information

Publication History

received 20 December 2013

accepted 11 March 2014

Publication Date:
07 April 2014 (online)

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Abstract

Advanced glycation end products (AGEs) and their receptor (RAGE) play a role in diabetic nephropathy. We have recently found that linagliptin, an inhibitor of dipeptidyl peptidase-4 (DPP-4) suppresses the AGE-induced oxidative stress generation and intercellular adhesion molecule-1 (ICAM-1) gene expression in endothelial cells. However, whether linagliptin could have beneficial effects on experimental diabetic nephropathy in a glucose-lowering independent manner remains unknown. To address the issue, this study examined the effects of linagliptin on renal damage in streptozotocin-induced diabetic rats. Serum levels of DPP-4 were significantly elevated in diabetic rats compared with control rats. Although linagliptin treatment for 2 weeks did not improve hyperglycemia in diabetic rats, linagliptin significantly reduced AGEs levels, RAGE gene expression, and 8-hydroxy-2′-deoxyguanosine, a marker of oxidative stress in the kidney of diabetic rats. Furthermore, linagliptin significantly reduced albuminuria, renal ICAM-1 mRNA levels, and lymphocyte infiltration into the glomeruli of diabetic rats. Our present study suggests that linagliptin could exert beneficial effects on diabetic nephropathy partly by blocking the AGE-RAGE-evoked oxidative stress generation in the kidney of streptozotocin-induced diabetic rats. Inhibition of DPP-4 by linagliptin might be a promising strategy for the treatment of diabetic nephropathy.

Key words

AGEs - RAGE - oxidative stress - DPP-4 - linagliptin - diabetic nephropathy
 

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