Molecular mechanisms of gastrointestinal hormone secretion by intestinal bacterial metabolites
| Project/Area Number |
17K08529
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
General physiology
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
TSUBOI Takashi 東京大学, 大学院総合文化研究科, 教授 (80415231)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
北口 哲也 東京工業大学, 科学技術創成研究院, 准教授 (60432374)
|
|---|
| Project Period (FY) |
2017-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | 開口分泌 / イメージング / 生理学 / シグナル伝達 / 消化管ホルモン |
|---|
| Outline of Final Research Achievements |
Glucagon-like peptide-1 (GLP-1), a gastrointestinal hormone, is secreted from enteroendocrine L cells in the small intestine. GLP-1 secretion is induced by various luminal nutrients, including amino acids and intestinal bacterial metabolites. However, the underlying mechanisms of intestinal bacterial metabolites-induced GLP-1 secretion are not well characterized. We investigated the mechanisms underlying the L-glutamine, one of the intestinal bacterial metabolite, induced GLP-1 secretion. We found that taste receptor type 1 member 3 (TAS1R3) was expressed in the L cells. We generated TAS1R3 mutant L cells using the CRISPR/Cas9 sysytem. TAS1R3 mutant L cells did not exhibited L-glutamine-induced GLP-1 secretion. Thus, these results suggest that TAS1R3 plays an important role in L-glutamine-induced GLP-1 secretion.
|
| Academic Significance and Societal Importance of the Research Achievements |
食餌由来成分である、糖、脂肪酸、アミノ酸によって小腸内分泌L細胞からグルカゴン様ペプチド-１（GLP-1）の分泌が促進されるが、その詳細な分泌促進分子機構は不明であった。本研究では、アミノ酸の中でもL-グルタミンによって起こるGLP-1分泌の促進が、うまみ受容体や甘味受容体を形成するTAS1R3によって制御されることを見出した。つまりL細胞は、消化管管腔内のケミカルセンサーとして機能している可能性がある。この結果は、GLP-1分泌を促す機能性食品の開発などにつながると考えられる。
|
Report
(5 results)
Research Products
(11 results)
-
-
[Journal Article] Green fluorescent protein-based lactate and pyruvate indicators suitable for biochemical assays and live cell imaging.2020
Author(s)
Harada K*, Chihara T*, Hayasaka Y*, Mita M, Takizawa M, Ishida K, Arai M, Tsuno S, Matsumoto M, Ishihara T, Ueda H, Kitaguchi T, Tsuboi T. *Equal contribution
-
Journal Title
Scientific Reports
Volume: 10
Issue: 1
Pages: 1-11
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
