Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8294280 | Biochemical and Biophysical Research Communications | 2018 | 7 Pages |
Abstract
This study aimed to evaluate the effects of combination therapy with a dipeptidyl peptidase-4 inhibitor, alogliptin, and a peroxisome proliferator-activated receptor-γ agonist, pioglitazone, in a preclinical model of nonalcoholic steatohepatitis using low-density lipoprotein receptor-knockout mice fed a modified choline-deficient l-amino acid-defined diet. Monotherapy with either alogliptin (10-200â¯mg/kg) or pioglitazone (6-20â¯mg/kg) significantly decreased hepatic triglyceride content and fibrosis. The concomitant treatment of alogliptin (30â¯mg/kg), pioglitazone (20â¯mg/kg) also decreased hepatic triglyceride and hepatic collagen-I mRNA at greater extent compared to monotherapy. Hepatic expression of CD11b mRNA and monocyte chemoattractant protein-1 were also reduced by the concomitant treatment. These results suggest that via an anti-inflammatory potential in addition to anti-metabolic effects, the combination therapy of alogliptin and pioglitazone may provide therapeutic benefits to type 2 diabetes patients with nonalcoholic steatohepatitis, which will be proven in controlled clinical trials.
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Authors
Yuichiro Amano, Shuntarou Tsuchiya, Mayumi Imai, Kimio Tohyama, Jun Matsukawa, Osamu Isono, Hironobu Yasuno, Kazuaki Enya, Emiko Koumura, Hiroshi Nagabukuro,