Dipeptidyl peptidase-4 inhibitor ameliorates early renal injury through its anti-inflammatory action in a rat model of type 1 diabetes.
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.
['Kodera|Ryo|R|', 'Shikata|Kenichi|K|', 'Takatsuka|Tetsuharu|T|', 'Oda|Kaori|K|', 'Miyamoto|Satoshi|S|', 'Kajitani|Nobuo|N|', 'Hirota|Daisho|D|', 'Ono|Tetsuichiro|T|', 'Usui|Hitomi Kataoka|HK|', 'Makino|Hirofumi|H|']
D000218:Adamantane D000818:Animals D000893:Anti-Inflammatory Agents D000242:Cyclic AMP D003921:Diabetes Mellitus, Experimental D003922:Diabetes Mellitus, Type 1 D003928:Diabetic Nephropathies D054873:Dipeptidyl-Peptidase IV Inhibitors D004195:Disease Models, Animal D052216:Glucagon-Like Peptide 1 D007674:Kidney Diseases D007678:Kidney Glomerulus D008297:Male D009570:Nitriles D020011:Protective Agents D011759:Pyrrolidines D051381:Rats D017207:Rats, Sprague-Dawley
Dipeptidyl peptidase-4 inhibitor dipeptidyl peptidase-4 DPP-4 glucagon-like peptide-1 GLP-1 Diabetic nephropathy SD cyclic AMP Macrophage nuclear factor-κB NF-κB CD CRP GIP ICAM-1 IL Inflammation PAM Sprague–Dawley TGF-β TNF-α c-reactive protein cAMP cluster of differentiation gastric inhibitory polypeptide intercellular adhesion molecule-1 interleukin periodic acid-methenamine silver transforming growth factor-β tumor necrosis factor-α