Lysophosphatidic acid receptor 4 as a potential drug target for the treatment of type 2 diabetes

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860169
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Akita University
• Principal Investigator: Ohto-N Takayo 秋田大学, 医学(系)研究科(研究院), 助教 (80511378)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: リゾホスファチジン酸

Outline of Final Research Achievements

Lysophosphatidic acid receptor 4 (LPA4)-deficient mice are resistant to high-fat diet-induced diabetes. This observation suggests that LPA4 antagonists may provide new therapeutic approaches for type 2 diabetes. Thus, the purpose of this project was to find LPA4 antagonists by screening a chemical library of Drug Discovery Initiative, The University of Tokyo.
I used rat neuroblastoma B103 cells, which lack endogenous responses to LPA, to assess the functions of LPA4. In contrast to the parental B103 cells, LPA4-expressing B103 cells (B103-LPA4) showed Ca2+ influx in response to LPA. By using B103-LPA4 cells, I identified 37 compounds that activate LPA4 predominantly. Furthermore, I examined commercially available two compounds, which were reported to be LPA4 antagonists, and their derivatives. However, no antagonist activities were detected in these compounds.

Free Research Field

脂質生物学