Evaluation of Teneligliptin Effects on Transcriptional Activity of PPARγ in Cell-Based Assays

J Nippon Med Sch. 2018;85(2):95-101. doi: 10.1272/jnms.2018_85-15.

Abstract

Background: The antidiabetic drug teneligliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor with a thiazolidine-specific structure. This study aimed to investigate whether teneligliptin can activate PPARγ directly and/or indirectly in cell-based assays.

Methods: Promoter assays using the reporter construct driven under the control of the SV40 promoter and the PPAR response element (PPRE) were performed. Luciferase activity was measured after a 3-day incubation of vector-transduced cells with various concentrations of teneligliptin.

Results: Treatment of the cells with 50 μM teneligliptin significantly transactivated a reporter gene. The presence of the PPARγ antagonist, GW9662, did not affect the activation of PPRE-reporter expression by teneligliptin.

Conclusion: We found that teneligliptin could increase PPARγ activity in cell-based assays irrespective of the PPARγ ligand-binding domain.

Keywords: adipogenesis; incretin; ligand; promoter assay; thiazolidinedione.

MeSH terms

  • Adipocytes / cytology
  • Anilides / pharmacology
  • Cell Differentiation / drug effects*
  • Cells, Cultured
  • Dipeptidyl-Peptidase IV Inhibitors / chemistry
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Ligands
  • Luciferases / metabolism
  • PPAR gamma / antagonists & inhibitors
  • PPAR gamma / genetics*
  • PPAR gamma / metabolism*
  • Protein Binding
  • Protein Domains
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Response Elements
  • Thiazolidines / chemistry
  • Thiazolidines / pharmacology*
  • Transcription, Genetic / drug effects*
  • Transcriptional Activation / drug effects

Substances

  • 2-chloro-5-nitrobenzanilide
  • 3-(4-(4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl)pyrrolidin-2-ylcarbonyl)thiazolidine
  • Anilides
  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Ligands
  • PPAR gamma
  • Pyrazoles
  • Thiazolidines
  • Luciferases