2021 Fiscal Year Final Research Report
Functional analysis of type 2 diabetes susceptibility genes in human pancreatic beta cells
| Project/Area Number |
18KK0438
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| Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
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| Allocation Type | Multi-year Fund |
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| Research Field |
Endocrinology
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| Research Institution | Kobe University |
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Principal Investigator |
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| Project Period (FY) |
2019 – 2021
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| Keywords | 膵β細胞 / 2型糖尿病 / エピジェネティクス |
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| Outline of Final Research Achievements |
In a previous study, the applicant showed in mice that mutations in the type 2 diabetes susceptibility gene Kcnq1 act to decrease pancreatic β-cell volume via down-regulation of a non-coding RNA called 'Kcnq1ot1'. In this study, we examined whether similar results were observed using human iPS cells and human pancreatic islets. When human iPS cells were induced to differentiate into pancreatic endocrine cells, Kcnq1ot1 expression was upregulated, but KCNQ1OT1 expression was downregulated in minor alleles of the KCNQ1 SNP. KCNQ1OT1 is also expressed in human islets, but the frequency of minor alleles of the KCNQ1 SNP is significantly lower in Westerners than in Japanese, so a comparative study was not possible.
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| Free Research Field |
代謝・内分泌学
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| Academic Significance and Societal Importance of the Research Achievements |
日本人は肥満が少ないにもかかわらず糖尿病患者が欧米並みに多い。これは膵β細胞が脆弱であることが原因と言われている。その原因遺伝子として重要と考えられるのがKCNQ1遺伝子である。KCNQ1遺伝子に特有の変異があるとインスリン分泌低下が見られるが、その機序は明らかではなかった。今回の代表者の研究成果により、KCNQ1遺伝子変異はKCNQ1OT1発現低下を介して糖尿病を発症させる可能性が示唆された。今後、KCNQ1OT1発現が2型糖尿病の治療や早期診断などの実臨床に応用されることが期待できる。
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