Combination of APD668, a G protein-coupled receptor 119 agonist with linagliptin, a DPPIV inhibitor, prevents progression of steatohepatitis in a ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-03

AUTHORS

Umakant Ashok Bahirat, Rashmi Talwar, Rekha Raghuveer Shenoy, Kumar V. S. Nemmani, Rajan Naresh Goel

ABSTRACT

Non-alcoholic steatohepatitis (NASH) is characterized by the presence of hepatic steatosis, oxidative stress, inflammation, and hepatocyte injury with or without fibrosis. In this study, we explored the effect of APD668, a GPR119 agonist alone or in combination with linagliptin, a DPPIV inhibitor, on the progression of steatohepatitis in a murine model of NASH with diabetes. A novel NASH model with diabetes was generated by administration of streptozotocin injection to neonatal C57BL/6 mice (2-3 days old) combined with a high-fat diet feeding from the age of 4 weeks. The plasma biochemical parameters, oxidative stress, inflammation and histopathological changes were assessed. APD668 alone showed reduction in plasma glucose (- 39%, P < 0.05) and triglyceride level (- 26%) whereas a combined treatment of APD668 with linagliptin resulted in a more pronounced reduction in plasma glucose (- 52%, P < 0.001) and triglyceride (- 50%, P < 0.05) in NASH mice. In addition, co-administration of APD668 with linagliptin demonstrated a significant decrease in hepatic triglyceride, NAS score, hepatic TBARS and hepatic TNF-α in NASH mice with diabetes. These findings suggest that GPR119 receptor agonists in combination with DPPIV inhibitors may represent a promising therapeutic strategy for the treatment of NASH. More... »

PAGES

36-43

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00795-018-0200-4

DOI

http://dx.doi.org/10.1007/s00795-018-0200-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1105218415

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29959534


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