TY - JOUR
T1 - Dipeptidyl peptidase-4 inhibitor ameliorates early renal injury through its anti-inflammatory action in a rat model of type 1 diabetes
AU - Kodera, Ryo
AU - Shikata, Kenichi
AU - Takatsuka, Tetsuharu
AU - Oda, Kaori
AU - Miyamoto, Satoshi
AU - Kajitani, Nobuo
AU - Hirota, Daisho
AU - Ono, Tetsuichiro
AU - Usui, Hitomi Kataoka
AU - Makino, Hirofumi
N1 - Funding Information:
This work was partially supported by research fund from Novartis Pharma K.K. KS receives speaker honoraria from Astellas, MSD, Eli Lilly Japan, Novartis Pharma, NovoNordisk, Ono, Sanofi and Tanabe Mitsubishi, and receives grant support from Tanabe Mitsubishi. HM is a consultant for AbbVie, Astellas, and Teijin, receives speaker honoraria from Astellas, MSD, Takeda, and Tanabe Mitsubishi, and receives grant support from Astellas, Daiichi Sankyo, Dainippon Sumitomo, MSD, Novo Nodisk, Takeda and Kyowahakko-Kirin.
PY - 2014/1/17
Y1 - 2014/1/17
N2 - 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.
AB - 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.
KW - Diabetic nephropathy
KW - Dipeptidyl peptidase-4 inhibitor
KW - Inflammation
KW - Macrophage
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U2 - 10.1016/j.bbrc.2013.12.049
DO - 10.1016/j.bbrc.2013.12.049
M3 - Article
C2 - 24342619
AN - SCOPUS:84893704282
VL - 443
SP - 828
EP - 833
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -
