Combination of APD668, a G protein-coupled receptor 119 agonist with linagliptin, a DPPIV inhibitor, prevents progression of steatohepatitis in a murine model of non-alcoholic steatohepatitis with diabetes

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalMedical Molecular Morphology
DOIs
Publication statusPublished - 29-06-2019

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Fatty Liver
G-Protein-Coupled Receptors
Triglycerides
Liver
Oxidative Stress
Inflammation
Glucose
High Fat Diet
Streptozocin
Linagliptin
Inbred C57BL Mouse
Hepatocytes
Fibrosis
Therapeutics
Injections
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology

Cite this

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title = "Combination of APD668, a G protein-coupled receptor 119 agonist with linagliptin, a DPPIV inhibitor, prevents progression of steatohepatitis in a murine model of non-alcoholic steatohepatitis with diabetes",
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.",
author = "Bahirat, {Umakant Ashok} and Rashmi Talwar and Shenoy, {Rekha Raghuveer} and Nemmani, {Kumar V.S.} and Goel, {Rajan Naresh}",
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AU - Talwar, Rashmi

AU - Shenoy, Rekha Raghuveer

AU - Nemmani, Kumar V.S.

AU - Goel, Rajan Naresh

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