| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2025-01-22 |
| タイトル |
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タイトル |
Oral Coadministration of Zn-Insulin with d-Form Small Intestine-Permeable Cyclic Peptide Enhances Its Blood Glucose-Lowering Effect in Mice |
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言語 |
en |
| 言語 |
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言語 |
eng |
| キーワード |
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主題 |
Cell-permeable peptide, Diabetes mellitus, Insulin, Insulin hexamer, Intestinal absorption |
| 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 |
| アクセス権 |
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アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 著者 |
Shingo, Ito
Yuta, Torii
Shoma, Chikamatsu
Tomonori, Harada
Shunsuke, Yamaguchi
Seiryo, Ogata
Kayoko, Sonoda
Tomohiko, Wakayama
Takeshi, Masuda
Sumio, Ohtsuki
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| 内容記述 |
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内容記述タイプ |
Abstract |
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内容記述 |
Oral delivery of insulin remains a challenge owing to its poor permeability across the small intestine and enzymatic digestion in the gastrointestinal tract. In a previous study, we identified a small intestine-permeable cyclic peptide, C-DNPGNET-C (C-C disulfide bond, cyclic DNP peptide), which facilitated the permeation of macromolecules. Here, we showed that intraintestinal and oral coadministration of insulin with the cyclic DNP derivative significantly reduced blood glucose levels by increasing the portal plasma insulin concentration following permeation across the small intestine of mice. We also found that protecting the cyclic DNP derivative from enzymatic digestion in the small intestine of mice using d-amino acids and by the cyclization of DNP peptide was essential to enhance cyclic DNP derivative-induced insulin absorption across the small intestine. Furthermore, intraintestinal and oral coadministration of insulin hexamer stabilized by zinc ions (Zn-insulin) with cyclic D-DNP derivative was more effective in facilitating insulin absorption and inducing hypoglycemic effects in mice than the coadministration of insulin with the cyclic D-DNP derivative. Moreover, Zn-insulin was more resistant to degradation in the small intestine of mice compared to insulin. Intraintestinal and oral coadministration of Zn-insulin with cyclic DNP derivative also reduced blood glucose levels in a streptozotocin-induced diabetes mellitus mouse model. A single intraintestinal administration of the cyclic D-DNP derivative did not induce any cytotoxicity, either locally in the small intestine or systemically. In summary, we demonstrated that coadministration of Zn-insulin with cyclic D-DNP derivative could enhance oral insulin absorption across the small intestine in mice. |
| bibliographic_information |
en : Molecular Pharmaceutics
巻 18,
号 4,
p. 1593-1603,
発行年 2021-04-05
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| item_16_source_id_7 |
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収録物識別子 |
1543-8384 |
| item_16_relation_11 |
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関連タイプ |
isVersionOf |
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関連識別子 |
https://doi.org/10.1021/acs.molpharmaceut.0c01010 |
| 権利 |
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権利情報 |
(C) 2021, American Chemical Society |
| 権利 |
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権利情報 |
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright (C) 2021, American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.molpharmaceut.0c01010 |
| 出版タイプ |
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出版タイプ |
AM |
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出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
| 出版者 |
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出版者 |
American Chemical Society |
10.1021_acs.molpharmaceut.0c01010.pdf (1.7 MB)
