Elucidation of genetic factors and mechanisms involved in the development and progression of type 2 diabetes using a novel rat model of the disease
Project/Area Number |
18H02364
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 42040:Laboratory animal science-related
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Research Institution | Kyoto University (2019-2020) Kobe University (2018) |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
谷口 幸雄 京都大学, 農学研究科, 准教授 (10252496)
波多野 直哉 神戸大学, 医学研究科, 医学研究員 (10332280)
須山 幹太 九州大学, 生体防御医学研究所, 教授 (70452365)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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Keywords | 糖尿病 / 疾患モデル / 遺伝素因 / 病態発症機構 / オミクス / 膵島障害 |
Outline of Final Research Achievements |
In this study, by using the Zucker fatty diabetes mellitus (ZFDM) rat, a novel rat model of type 2 diabetes which has been developed by the representative researcher’s group, we performed genetic analysis and exome analysis to identify diabetes susceptibility genes, CRISPR/Cas9-mediated genome editing of the candidate gene to verify the causality, mRNA-sequencing and metabolome analysis to elucidate longitudinal changes in metabolic dysfunction, and proteome analysis to identify abnormally modified proteins, resulting in the clarification of a part of genetic factors and mechanisms involved in the development and progression of the disease.
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Academic Significance and Societal Importance of the Research Achievements |
本研究により明らかとなったZFDMラットにおける遺伝素因と膵島障害の発症・進展機構は、ヒト糖尿病の遺伝素因と病態発症・進展機構の解明や新規のメカニズムに基づく治療薬の開発の基盤となると考えられる。また、同様の研究手法が適用可能な様々の研究分野において疾患モデルの有用性を実証するものである。
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Report
(4 results)
Research Products
(28 results)
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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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[Journal Article] Tumor-like features of gene expression and metabolic profiles in enlarged pancreatic islets are associated with impaired incretin-induced insulin secretion in obese diabetes: a study of ZFDM rat.2020
Author(s)
Hayami T, Yokoi N, Yamaguchi T, Honda K, Murao N, Takahashi H, Wang S, Seino Y, Kamiya H, Yabe D, Sweet IR, Mizoguchi A, Nakamura J, Seino S
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Journal Title
J Diabetes Investig
Volume: -
Issue: 6
Pages: 1434-1447
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Gs/Gq signaling switch in β cells defines incretin effectiveness in diabetes2020
Author(s)
Oduori Okechi S.、Murao Naoya、Shimomura Kenju、Takahashi Harumi、Zhang Quan、Dou Haiqiang、Sakai Shihomi、Minami Kohtaro、Chanclon Belen、Guida Claudia、Kothegala Lakshmi、Tol? Johan、Maejima Yuko、Yokoi Norihide、Minami Yasuhiro、Miki Takashi、Rorsman Patrik、Seino Susumu
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Journal Title
Journal of Clinical Investigation
Volume: 130
Issue: 12
Pages: 6639-6655
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Functional adenosine triphosphate-sensitive potassium channel is required in high-carbohydrate diet-induced increase in β-cell mass.2019
Author(s)
Murase M, Seino Y, Maekawa R, Iida A, Hosokawa K, Hayami T, Tsunekawa S, Hamada Y, Yokoi N, Seino S, Hayashi Y, Arima H
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Journal Title
J Diabetes Investig
Volume: 10(2)
Issue: 2
Pages: 238-250
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Gs to Gq signaling switch in b-cells due to persistent depolarization determines effective insulin secretion-based drugs2020
Author(s)
Okechi OS, Murao N, Shimomura K, Zhang Q, Dou H, Takahashi H, Maejima Y, Minami K, Yokoi N, Miki T, Rorsman P, Seino S
Organizer
第63回日本糖尿病学会年次学術集会
Related Report
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[Presentation] 肥満糖尿病の膵島におけるインクレチン応答性障害―オミクス解析による検討―2018
Author(s)
速水智英, 横井伯英, 日高志保美, 川畑綾子, グプルジャン ゲニ, マヒラ アシム, 高橋晴美, 神谷英紀, 清野 裕, 中村二郎, 清野 進
Organizer
第61回日本糖尿病学会年次学術集会
Related Report
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