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

Abstract

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.

• Authors: Ryo Kodera, Kenichi Shikata, Tetsuharu Takatsuka, Kaori Oda, Satoshi Miyamoto, Nobuo Kajitani, Daisho Hirota, Tetsuichiro Ono, Hitomi Kataoka Usui, Hirofumi Makino
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 443 Issue 3 Pg. 828-33 (Jan 17 2014) ISSN: 1090-2104 [Electronic] United States
• PMID: 24342619 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Chemical References

• 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

Topics

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