Dipeptidyl peptidase-4 inhibitor ameliorates early renal injury through its anti-inflammatory action in a rat model of type 1 diabetes

Biochem Biophys Res Commun. 2014 Jan 17;443(3):828-33. doi: 10.1016/j.bbrc.2013.12.049. Epub 2013 Dec 14.


Introduction: 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.

Materials and 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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / analogs & derivatives
  • Adamantane / pharmacology
  • Adamantane / therapeutic use
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Cyclic AMP / urine
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / complications
  • Diabetic Nephropathies / drug therapy
  • Diabetic Nephropathies / pathology
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Disease Models, Animal
  • Glucagon-Like Peptide 1 / blood
  • Kidney Diseases / complications
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / pathology
  • Male
  • Nitriles / pharmacology
  • Nitriles / therapeutic use
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use
  • Pyrrolidines / pharmacology
  • Pyrrolidines / therapeutic use
  • Rats
  • Rats, Sprague-Dawley


  • 1-((2-adamantyl)amino)acetyl-2-cyano-(S)-pyrrolidine, monohydrochloride
  • Anti-Inflammatory Agents
  • Dipeptidyl-Peptidase IV Inhibitors
  • Nitriles
  • Protective Agents
  • Pyrrolidines
  • Glucagon-Like Peptide 1
  • Cyclic AMP
  • Adamantane