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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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
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| Keywords | 膵β細胞 / 2型糖尿病 / エピジェネティクス / ヒト膵島 / 2型糖尿病感受性遺伝子 / ２型糖尿病感受性遺伝子 / 可塑性 / ヒトiPS細胞 |
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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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| 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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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Oral administration of D-serine prevents the onset and progression of colitis in mice.2021
Author(s)
Takehito Asakawa, Michio Onizawa, Chikako Saito, Rie Hikichi, Daiki Yamada, Ai Minamidate, Tomoaki Mochimaru, Shun-ichiro Asahara, Yoshiaki Kido, Shigeru Oshima, Takashi Nagaishi, Kiichiro Tsuchiya, Hiromasa Ohira, Ryuichi Okamoto, Mamoru Watanabe.
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Journal Title
Journal of Gastroenterolog.
Volume: 56
Issue: 8
Pages: 732-745
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] GCN2 regulates pancreatic β-cell mass by sensing intracellular amino acid levels.2020
Author(s)
Kanno A, Asahara SI, Furubayashi A, Masuda K, Yoshitomi R, Suzuki E, Takai T, Kimura-Koyanagi M, Matsuda T, Bartolome A, Hirota Y, Yokoi N, Inaba Y, Inoue H, Matsumoto M, Inoue K, Abe T, Wei FY, Tomizawa K, Ogawa W, Seino S, Kasuga M, Kido Y.
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Journal Title
JCI Insight.
Volume: 5
Issue: 9
Pages: 128820-128820
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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