title: Renoprotective effect of DPP-4 inhibitors against free fatty acid-bound albumin-induced renal proximal tubular cell injury.
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.
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Tsukinokawa-Cho, Seta, Otsu, Shiga, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Tsukinokawa-Cho, Seta, Otsu, Shiga, Japan. Electronic address: skume@belle.shiga-med.ac.jp.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kume
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Tsukinokawa-Cho, Seta, Otsu, Shiga, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Chin-Kanasaki
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Tsukinokawa-Cho, Seta, Otsu, Shiga, Japan.
authors.forename: Hisazumi
authors.initials: H
authors.lastname: Araki
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Tsukinokawa-Cho, Seta, Otsu, Shiga, Japan.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Araki
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Tsukinokawa-Cho, Seta, Otsu, Shiga, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ugi
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sugaya
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Tsukinokawa-Cho, Seta, Otsu, Shiga, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Uzu
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Tsukinokawa-Cho, Seta, Otsu, Shiga, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maegawa
mesh_terms: D000418:Albumins; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016896:Treatment Outcome
chemical_list: D000418:Albumins; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005230:Fatty Acids, Nonesterified; D018819:Dipeptidyl Peptidase 4; C545245:Dpp4 protein, mouse
keywords: Albuminuria; DPP–4 inhibitors; Diabetic nephropathy; Free fatty acid; Proximal tubular cell