Analysis of pathogenic mechanism by susceptibility genes of T2DM using human iPS cells.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09882
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Kobe University
• Principal Investigator: Asahara] Shun-ichiro 神戸大学, 医学部附属病院, 助教 (00570342)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ヒトiPS細胞 / 糖尿病 / 膵β細胞

Outline of Final Research Achievements

It has been previously reported that KCNQ1 and EIF2AK4 were identified as T2DM susceptibility genes. We have clarified that the reduction of non-coding RNA Kcnq1ot1 expression induced pancratic beta cell failure in Kcnq1 mutant mice. Now, we analyzed the mechanism how T2DM susceptibility gene induces diabetes using human iPS cells derived pancreatic endocrine cell. As a result, we clarified that two iPS cells were differentiated into pancreatic endocrine cells. One cell has a risk allele of T2DM susceptibility gene, and the other without risl allele. The hiPS cell with a risk allele showed a reduced expression of Kcnq1ot1 compared to pancreatic endocrine cell without a risk allele.

Free Research Field

糖尿病学

Academic Significance and Societal Importance of the Research Achievements

今回の研究により、KCNQ1遺伝子において2型糖尿病発症のリスク因子となるSNPはKcnq1ot1発現低下に影響している可能性が考えられた。我々のこれまでの研究成果より、膵β細胞におけるp57発現増加が膵β細胞不全を介して2型糖尿病発症に繋がっていることがヒト細胞においても証明された。この結果、KCNQ1遺伝子のリスクアリルとなるSNPは2型糖尿病発症の予測因子として重要であり、将来的に検査項目の一つとなることが期待される。