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.
Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.