Identify the novel bioactive peptides and their role in feeding regulation
| Project/Area Number |
16H05333
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | University of Miyazaki |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
上野 浩晶 宮崎大学, 医学部, 助教 (00381062)
山口 秀樹 宮崎大学, 医学部, 講師 (10305097)
迫田 秀之 宮崎大学, 医学部, 講師 (50376464)
柳 重久 宮崎大学, 医学部, 助教 (60404422)
坪内 拡伸 宮崎大学, 医学部, 助教 (60573988)
清水 浩一郎 宮崎大学, 医学部, その他 (90711292)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | 生理活性ペプチド / 摂食中枢 / 肥満 / 糖脂質代謝 / ペプチドホルモン / 内分泌学 |
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| Outline of Final Research Achievements |
GHSR is selectively expressed in the hindbrain and vagus nerve of Phox2B-GHSR mice. GHSR-expressing neurons in the nodose ganglion are less abundant in the mice than in wild-type mice. Intraperitoneal ghrelin administration did not induce food intake or growth hormone release, suggesting that the abundance of GHSR-expressing neurons is critical for peripheral ghrelin action.
NMU acts directly on β cells through NMUR1 in an autocrine or paracrine fashion to suppress insulin secretion. NMU also induces mitochondrial dysfunction and ER stress, eventually leading to impaired β-cell functions.
Ghrelin’s orexigenic activity was abolished after 2-4 weeks HFD-fed mice, consistent with the timing of accumulation and activation of macrophage/microglia in the nodose ganglion and hypothalamus. Calorie-restricted weight loss restored ghrelin responsiveness and alleviated the upregulation of macrophage/microglia activation markers and inflammatory cytokines in the nodose ganglion and hypothalamus.
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| Academic Significance and Societal Importance of the Research Achievements |
ペプチドによる生体制御と病態との関連解析、そして治療応用に至る一貫した成果に基づく申請である。末梢からのペプチド情報が経神経性に脳内の特定の部位に伝達され、自律神経を介して免疫系を調節している。過栄養や糖代謝異常による慢性炎症が、迷走神経節や視床下部にも及び、ペプチド受容体の発現低下から摂食行動の異常に至る分子機序を明らかにした。
膵β細胞にオートクリン、パラクリンとして作用してインスリン分泌を調節し、膵β細胞の維持や機能に重要な役割を果たすペプチドの解析は、糖尿病の病態理解と新規の治療法開発につながることが期待できる。
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Report
(4 results)
Research Products
(43 results)
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[Journal Article] Activation of AMPK-Regulated CRH Neurons in the PVH is Sufficient and Necessary to Induce Dietary Preference for Carbohydrate over Fat.2018
Author(s)
Okamoto S, Sato T, Tateyama M, Kageyama H, Maejima Y, Nakata M, Hirako S, Matsuo T, Kyaw S, Shiuchi T, Toda C, Sedbazar U, Saito K, Asgar NF, Zhang B, Yokota S, Kobayashi K, Foufelle F, Ferré P, Nakazato M, Masuzaki H, Shioda S, Yada T, Kahn BB, Minokoshi Y.
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Journal Title
Cell Rep.
Volume: 22
Issue: 3
Pages: 706-721
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Canagliflozin, a sodium glucose cotransporter 2 inhibitor, attenuates obesity-induced inflammation in the nodose ganglion, hypothalamus, and skeletal muscle of mice2016
Author(s)
Naznin F, Sakoda H, Okada T, Tsubouchi H, Waise TM, Arakawa K, Nakazato M
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Journal Title
Eur J Pharmacol
Volume: 794
Pages: 37-44
DOI
Related Report
Peer Reviewed / Open Access
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