Identification of the gene that causes insulin resistance syndrome using exome sequencing and iPS cells.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09750
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kobe University
• Principal Investigator: Hirota Yushi 神戸大学, 医学部附属病院, 助教 (80566018)
• Research Collaborator: Ogawa Wataru ; Aoi Takashi ; Satake Wataru
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: インスリン抵抗症 / エクソーム解析 / iPS細胞 / SHORT症候群 / PIK3R1遺伝子

Outline of Final Research Achievements

As a result of exome analysis aiming at identification of the causative gene of the insulin resistance family, PIK3R1 gene c.1945C> T mutation was identified.
In order to clarify the function of this mutation, we established iPS cells from probands and induced differentiation into hepatocytes. Compared with hepatocytes derived from healthy person-derived iPS cells, Akt phosphorylation upon addition of insulin was significantly suppressed, suggesting that the PIK3R1 abnormality suppresses the insulin action.

Free Research Field

糖代謝

Academic Significance and Societal Importance of the Research Achievements

本インスリン抵抗症家系の原因遺伝子はPIK3R1遺伝子であったが、SHORT症候群の原因遺伝子として海外から2013年に報告されていた。しかし日本人を初めとした東アジア人では初の報告となり、顔貌などの特徴が世界共通であることが明らかとなった。また、PIK3R1遺伝子の疾患iPS細胞を作成したが、この疾患iPS細胞は世界で始めてのものであり意義は大きい。