| Item type |
デフォルトアイテムタイプ_（フル）(1) |
| 公開日 |
2023-03-18 |
| タイトル |
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|
タイトル |
Trk-fused gene (TFG) regulates pancreatic beta cell mass and insulin secretory activity |
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言語 |
en |
| 作成者 |
Yamamotoya, Takeshi
Nakatsu, Yusuke
Kushiyama, Akifumi
Matsunaga, Yasuka
Ueda, Koji
Inoue, Yuki
Inoue, Masa-Ki
Sakoda, Hideyuki
Fujishiro, Midori
Ono , Hiraku
Kiyonari, Hiroshi
Ishihara, Hisamitsu
Asano, Tomoichiro
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| アクセス権 |
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アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 権利情報 |
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|
権利情報 |
© The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| 内容記述 |
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内容記述 |
The Trk-fused gene (TFG) is reportedly involved in the process of COPII-mediated vesicle transport and missense mutations in TFG cause several neurodegenerative diseases including hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P). The high coincidence ratio between HMSN-P and diabetes mellitus suggests TFG to have an important role(s) in glucose homeostasis. To examine this possibility, β-cell specific TFG knockout mice (βTFG KO) were generated. Interestingly, βTFG KO displayed marked glucose intolerance with reduced insulin secretion. Immunohistochemical analysis revealed smaller β-cell masses in βTFG KO than in controls, likely attributable to diminished β-cell proliferation. Consistently, β-cell expansion in response to a high-fat, high-sucrose (HFHS) diet was significantly impaired in βTFG KO. Furthermore, glucose-induced insulin secretion was also markedly impaired in islets isolated from βTFG KO. Electron microscopic observation revealed endoplasmic reticulum (ER) dilatation, suggestive of ER stress, and smaller insulin crystal diameters in β-cells of βTFG KO. Microarray gene expression analysis indicated downregulation of NF-E2 related factor 2 (Nrf2) and its downstream genes in TFG depleted islets. Collectively, TFG in pancreatic β-cells plays a vital role in maintaining both the mass and function of β-cells, and its dysfunction increases the tendency to develop glucose intolerance. |
|
言語 |
en |
| 内容記述 |
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|
内容記述タイプ |
Other |
|
内容記述 |
This study was partly supported by a Grant-in-Aid for Research Activity Start-up (JSPS KAKENHI Grant Number JP15H06427) (to T.Y.) from the Ministry of Education, Science, Sports and Culture, Japan, and grants from Mitsubishi Tanabe Pharma (to T.Y.), Novartis Pharma (to T.Y.), Takeda Science Foundation (to Y.N.), Asahi Life Foundation (to Y.N.) and The Uehara Memorial Foundation (to Y.N.). |
| 出版者 |
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出版者 |
Nature Research |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 出版タイプ |
|
|
出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 関連情報 |
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|
識別子タイプ |
DOI |
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関連識別子 |
10.1038/s41598-017-13432-x |
| 関連情報 |
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|
識別子タイプ |
PMID |
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関連識別子 |
29026155 |
| 関連情報 |
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|
識別子タイプ |
DOI |
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|
関連識別子 |
https://doi.org/10.1038/s41598-017-13432-x |
| 収録物識別子 |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
0002-7863 |
| 開始ページ |
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開始ページ |
13026 |
| 書誌情報 |
Scientific Reports
Scientific Reports
巻 7,
p. 13026,
発行日 2017-10-12
|
| 旧ID |
48641 |
SciRep_7_13026.pdf (6.5 MB)
