title: Dipeptidyl peptidase-4 inhibitor ameliorates early renal injury through its anti-inflammatory action in a rat model of type 1 diabetes.
abstract: BACKGROUND
  Dipeptidyl peptidase-4 (DPP-4) inhibitors are incretin-based drugs in patients with type 2 diabetes. In our previous study, we showed that glucagon-like peptide-1 (GLP-1) receptor agonist has reno-protective effects through anti-inflammatory action. The mechanism of action of DPP-4 inhibitor is different from that of GLP-1 receptor agonists. It is not obvious whether DPP-4 inhibitor prevents the exacerbation of diabetic nephropathy through anti-inflammatory effects besides lowering blood glucose or not. The purpose of this study is to clarify the reno-protective effects of DPP-4 inhibitor through anti-inflammatory actions in the early diabetic nephropathy.
  
  
  METHODS
  Five-week-old male Sprague-Dawley (SD) rats were divided into three groups; non-diabetes, diabetes and diabetes treated with DPP-4 inhibitor (PKF275-055; 3 mg/kg/day). PKF275-055 was administered orally for 8 weeks.
  
  
  RESULTS
  PKF275-055 increased the serum active GLP-1 concentration and the production of urinary cyclic AMP. PKF275-055 decreased urinary albumin excretion and ameliorated histological change of diabetic nephropathy. Macrophage infiltration was inhibited, and inflammatory molecules were down-regulated by PKF275-055 in the glomeruli. In addition, nuclear factor-κB (NF-κB) activity was suppressed in the kidney.
  
  
  CONCLUSIONS
  These results indicate that DPP-4 inhibitor, PKF275-055, have reno-protective effects through anti-inflammatory action in the early stage of diabetic nephropathy. The endogenous biological active GLP-1 might be beneficial on diabetic nephropathy besides lowering blood glucose.
authors.affiliation: Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. Electronic address: kodera@cc.okayama-u.ac.jp.
authors.forename: Ryo
authors.initials: R
authors.lastname: Kodera
authors.affiliation: Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan; Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shikata
authors.affiliation: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Tetsuharu
authors.initials: T
authors.lastname: Takatsuka
authors.affiliation: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Oda
authors.affiliation: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Miyamoto
authors.affiliation: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Kajitani
authors.affiliation: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Daisho
authors.initials: D
authors.lastname: Hirota
authors.affiliation: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Tetsuichiro
authors.initials: T
authors.lastname: Ono
authors.affiliation: Department of Primary Care and Medical Education, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Hitomi Kataoka
authors.initials: HK
authors.lastname: Usui
authors.affiliation: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Makino
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000242:Cyclic AMP / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D007674:Kidney Diseases / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D008297:Male; D009570:Nitriles / Q000494:pharmacology / Q000627:therapeutic use; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D011759:Pyrrolidines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C569631:1-((2-adamantyl)amino)acetyl-2-cyano-(S)-pyrrolidine, monohydrochloride; D000893:Anti-Inflammatory Agents; D054873:Dipeptidyl-Peptidase IV Inhibitors; D009570:Nitriles; D020011:Protective Agents; D011759:Pyrrolidines; D052216:Glucagon-Like Peptide 1; D000242:Cyclic AMP; D000218:Adamantane
keywords: CD; CRP; DPP-4; Diabetic nephropathy; Dipeptidyl peptidase-4 inhibitor; GIP; GLP-1; ICAM-1; IL; Inflammation; Macrophage; NF-κB; PAM; SD; Sprague–Dawley; TGF-β; TNF-α; c-reactive protein; cAMP; cluster of differentiation; cyclic AMP; dipeptidyl peptidase-4; gastric inhibitory polypeptide; glucagon-like peptide-1; intercellular adhesion molecule-1; interleukin; nuclear factor-κB; periodic acid-methenamine silver; transforming growth factor-β; tumor necrosis factor-α