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Biochem Biophys Res Commun. 2016 Feb 12;470(3):539-545. doi: 10.1016/j.bbrc.2016.01.109. Epub 2016 Jan 21.

Renoprotective effect of DPP-4 inhibitors against free fatty acid-bound albumin-induced renal proximal tubular cell injury.

Author information

1
Department of Medicine, Shiga University of Medical Science, Tsukinokawa-Cho, Seta, Otsu, Shiga, Japan.
2
Department of Medicine, Shiga University of Medical Science, Tsukinokawa-Cho, Seta, Otsu, Shiga, Japan. Electronic address: skume@belle.shiga-med.ac.jp.
3
Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan.

Abstract

Dipeptidyl peptidase (DPP)-4 inhibitors, a new class of antidiabetic agent, have recently been suggested to exert pleiotropic effects beyond glucose lowering. Renal prognosis in patients with diabetic nephropathy depends on the severity of tubulointerstitial injury induced by massive proteinuria. We thus examined the renoprotective effect of DPP-4 inhibitors on inflammation in cultured mouse proximal tubular cells stimulated with free fatty acid (FFA)-bound albumin. Linagliptin and higher concentrations of sitagliptin, vildagliptin, and alogliptin all inhibited FFA-bound albumin-induced increases in mRNA expression of MCP-1 in cultured mouse proximal tubular cells. Furthermore, linagliptin significantly inhibited tubulointerstitial injury induced by peritoneal injection of FFA-bound albumin, such as inflammation, fibrosis, and apoptosis, in mice without altering systemic characteristics including body weight, fasting blood glucose, and food intake. These results indicate that DPP-4 inhibitors pleiotropically exert a direct renoprotective effect, and may serve as an additional therapeutic strategy to protect proximal tubular cells against proteinuria in patients with diabetic nephropathy.

KEYWORDS:

Albuminuria; DPP–4 inhibitors; Diabetic nephropathy; Free fatty acid; Proximal tubular cell

PMID:
26802469
DOI:
10.1016/j.bbrc.2016.01.109
[Indexed for MEDLINE]

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