| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2024-09-27 |
| タイトル |
|
|
タイトル |
Development of a long acting FGF21 analogue-albumin fusion protein and its anti-diabetic effects |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| キーワード |
|
|
主題 |
FGF21, Albumin-fusion, Adipocyte, Diabetes, GLUT1 |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 著者 |
Watanabe, Hiroshi
Miyahisa, Masako
Chikamatsu, Mayuko
Nishida, Kento
Minayoshi, Yuki
Takano, Mei
Ichimizu, Shota
Kobashigawa, Yoshihiro
Morioka, Hiroshi
Maeda, Hitoshi
Maruyama, Toru
|
| 内容記述 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Fibroblast growth factor 21 (FGF21) is a hormone-like protein that improves blood glucose and lipid metabolism. However, its short half-life and instability are bottlenecks to its clinical applications. In this study, to extend its pharmacological action, we created a stabilized mutant FGF21 (mFGF21:ΔHPIP, P171G, A180E, L118C-A134C, S167A) and then genetically fused it with human albumin (HSA-mFGF21) via a polypeptide linker. Physicochemical analyses suggested that HSA-mFGF21 was formed from both intact HSA and mFGF21. Pharmacokinetic findings indicated the half-life of HSA-mFGF21 was 20 times longer than that of FGF21. In addition, HSA-mFGF21 was persistently distributed in adipose tissue as a target tissue. The in vivo hypoglycemic activity of HSA-mFGF21 using streptozotocin (STZ)-induced type I diabetes model mice, in which insulin secretion was suppressed, showed that a single intravenous administration of HSA-mFGF21 rapidly alleviated hyperglycemia. At that time, HSA-mFGF21 increased GLUT1 mRNA expression in adipose tissue without having any effect on insulin secretion. A twice weekly administration of HSA-mFGF21 continuously suppressed blood glucose levels and ameliorated the abnormalities of adipose tissue induced by STZ treatment. Interestingly, HSA-mFGF21 showed no hypoglycemic effects in healthy mice. Together, HSA-mFGF21 could be a novel biotherapeutic for the treatment of metabolic disorders including diabetes mellitus. |
| bibliographic_information |
en : Journal of Controlled Release
巻 324,
p. 522-531,
発行年 2020-08-10
|
| item_16_source_id_7 |
|
|
収録物識別子 |
0168-3659 |
| 権利 |
|
|
権利情報 |
(C) 2020 Elsevier B.V. All rights reserved. |
| 権利 |
|
|
権利情報 |
This manuscript version is made available under the CC-BY-NC-ND 4.0 license. https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| 出版タイプ |
|
|
出版タイプ |
AM |
|
出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
| 出版者 |
|
|
出版者 |
Elsevier |
| 関連 |
|
|
関連タイプ |
isVersionOf |
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1016/j.jconrel.2020.05.036 |
10.1016_j.jconrel.2020.05.036.pdf (731 KB)
.png)
