scholarly journals Combined treatment with dipeptidyl peptidase-4 inhibitor (sitagliptin) and angiotensin-II type 1 receptor blocker (losartan) suppresses progression in a non-diabetic rat model of steatohepatitis

2017 ◽  
Vol 47 (12) ◽  
pp. 1317-1328 ◽  
Author(s):  
Yasushi Okura ◽  
Tadashi Namisaki ◽  
Kei Moriya ◽  
Mitsuteru Kitade ◽  
Kosuke Takeda ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Rat Model ◽  
Combined Treatment ◽  
Dipeptidyl Peptidase ◽  
Receptor Blocker ◽  
Diabetic Rat ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitor ◽  
Diabetic Rat Model

scholarly journals Combined Treatment with Sodium-Glucose Cotransporter-2 Inhibitor (Canagliflozin) and Dipeptidyl Peptidase-4 Inhibitor (Teneligliptin) Alleviates NASH Progression in A Non-Diabetic Rat Model of Steatohepatitis

2020 ◽  
Vol 21 (6) ◽  
pp. 2164
Author(s):  
Takahiro Ozutsumi ◽  
Tadashi Namisaki ◽  
Naotaka Shimozato ◽  
Kosuke Kaji ◽  
Yuki Tsuji ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Cell Proliferation ◽  
Combined Treatment ◽  
Diabetic Rat ◽  
Hepatic Lipid ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitor ◽  
Hepatic Lipid Peroxidation ◽  
Diabetic Rat Model

Hepatocellular carcinoma (HCC) is the strongest independent predictor of mortality in non-alcoholic steatohepatitis (NASH)-related cirrhosis. The effects and mechanisms of combination of sodium-dependent glucose cotransporter inhibitor and canagliflozin (CA) and dipeptidyl peptidase-4 inhibitor and teneligliptin (TE) on non-diabetic NASH progression were examined. CA and TE suppressed choline-deficient, L-amino acid-defined diet-induced hepatic fibrogenesis and carcinogenesis. CA alone or with TE significantly decreased proinflammatory cytokine expression. CA and TE significantly attenuated hepatic lipid peroxidation. In vitro studies showed that TE alone or with CA inhibited cell proliferation and TGF-β1 and α1 (I)-procollagen mRNA expression in Ac-HSCs. CA+TE inhibited liver fibrogenesis by attenuating hepatic lipid peroxidation and inflammation and by inhibiting Ac-HSC proliferation with concomitant attenuation of hepatic lipid peroxidation. Moreover, CA+TE suppressed in vivo angiogenesis and oxidative DNA damage. CA or CA+TE inhibited HCC cells and human umbilical vein endothelial cell (HUVEC) proliferation. CA+TE suppressed vascular endothelial growth factor expression and promoted increased E-cadherin expression in HUVECs. CA+TE potentially exerts synergistic effects on hepatocarcinogenesis prevention by suppressing HCC cell proliferation and angiogenesis and concomitantly reducing oxidative stress and by inhibiting angiogenesis with attenuation of oxidative stress. CA+TE showed chemopreventive effects on NASH progression compared with single agent in non-diabetic rat model of NASH, concurrent with Ac-HSC and HCC cell proliferation, angiogenesis oxidative stress, and inflammation. Both agents are widely, safely used in clinical practice; combined treatment may represent a potential strategy against NASH.

The dipeptidyl peptidase 4 inhibitor sitagliptin improves oxidative stress and ameliorates glomerular lesions in a rat model of type 1 diabetes

Life Sciences ◽  
2019 ◽  
Vol 234 ◽  
pp. 116738 ◽  
Author(s):  
Catarina Marques ◽  
Andreia Gonçalves ◽  
Patrícia Manuela Ribeiro Pereira ◽  
Daniela Almeida ◽  
Beatriz Martins ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 1 Diabetes ◽  
Rat Model ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitor ◽  
Glomerular Lesions

scholarly journals Linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor, ameliorates experimental autoimmune myocarditis by suppressing cathepsin-G activity

2020 ◽  
Author(s):  
Yuka Shiheido-Watanabe ◽  
Yasuhiro Maejima ◽  
Shun Nakagama ◽  
Natsuko Tamura ◽  
Takeshi Kasama ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Th17 Cells ◽  
Underlying Mechanism ◽  
Dipeptidyl Peptidase ◽  
Cathepsin G ◽  
Autoimmune Myocarditis ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitor ◽  
Experimental Autoimmune Myocarditis ◽  
Experimental Autoimmune

Abstract Background There is a compelling need for establishing effective therapy for autoimmune myocarditis which primarily manifest as chest pain, heart failure or sudden death. Although our group have previously shown that dipeptidyl peptidase-4 (DPP-4) aggravates experimental autoimmune myocarditis (EAM), the detailed underlying mechanism remains to be unelucidated. Methods The effects of linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor, on cardiac function were investigated by treating mouse EAM models and elucidated the role of DPP-4 on EAM using proteomic approaches. Results Immunohistochemical analyses demonstrated that the number of Th17 cells expressing high level of DPP-4 infiltrated to EAM myocardium was significantly attenuated by linagliptin treatment. MS/MS-based analyses demonstrated that DPP-4 binds to cathepsin-G in EAM hearts. DPP-4 also protects cathepsin-G activity by inhibiting the activity of SerpinA3N, a protease inhibitor that catalyzes cathepsin-G. The activity of cathepsin-G and the level of Angiotensin II were markedly elevated in EAM myocardium; this effect was reversed by linagliptin treatment. Furthermore, we found that linagliptin suppresses oxidative stress in EAM hearts. Conclusions DPP-4 physically interacts with cathepsin-G, which, in turn, suppresses SerpinA3N; this promotes angiotensin II accumulation in EAM hearts. Thus, DPP-4 derived from Th17 cells could aggravate cardiac dysfunction during EAM.

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