-Original-

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

Yasuhiro Takenaka¹, Ikuo Inoue², Takanari Nakano³, Masaaki Ikeda⁴, Yoshihiko Kakinuma¹, Yuichi Ikegami², Akira Shimada² and Mitsuhiko Noda²

¹Department of Physiology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
²Department of Diabetes and Endocrinology, Saitama Medical University, Saitama, Japan
³Department of Biochemistry, Saitama Medical University, Saitama, Japan
⁴Department of Physiology, Saitama Medical University, Saitama, Japan

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.

J Nippon Med Sch 2018; 85: 95-101

Keywords
thiazolidinedione, incretin, ligand, adipogenesis, promoter assay

Correspondence to
Yasuhiro Takenaka, PhD, Department of Physiology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan
yasuhiro-takenaka@nms.ac.jp

Received, November 11, 2017
Accepted, December 12, 2017