Establishment of an assay system for the drug-development of type 2 diabetes mellitus using iPS cells from a patient with human insulin receptor gene defect

2016 Fiscal Year Final Research Report

• Project/Area Number: 26670509
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Keio University
• Principal Investigator: Nakae Jun 慶應義塾大学, 医学部(信濃町), 特任准教授 (00344573)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: iPS細胞 / インスリン受容体異常症 / Foxo1 / 低分子化合物 / ハイスループットスクリーニング

Outline of Final Research Achievements

In order to generate human insulin-resistant cells, we try to establish human iPS cells derived from a patient with insulin receptor gene mutations (Leprechaunism) and to differentiate them into insulin responsive cells, including hepatocytes or adipocytes. After establishment of them, we investigate the effects of low molecular weight chemicals that inhibits Foxo1 transcriptional activity using these cells because Foxo1 activity in these cells are active due to defects of insulin signaling.
We could establish human iPS cells from a patient with Leprechaunism but not make them differentiate into insulin-responsive hepatocyte and adipocytes. However, I could have nine low molecular weight chemicals that activate or inhibit Foxo1 transcriptional activity. Therefore, we will continue to identify chemicals for therapy of type 2 diabetes mellitus.

Free Research Field

肥満　２型糖尿病