Synthetic "smart gel" provides glucose-responsive insulin delivery in diabetic mice

Akira Matsumoto, Miyako Tanaka, Hiroko Matsumoto, Kozue Ochi, Yuki Moro-Oka, Hirohito Kuwata, Hironori Yamada, Ibuki Shirakawa, Taiki Miyazawa, Hitoshi Ishii, Kazunori Kataoka, Yoshihiro Ogawa, Yuji Miyahara, Takayoshi Suganami

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

Although previous studies have attempted to create "electronics-free" insulin delivery systemsusing glucose oxidase and sugar-binding lectins as a glucose-sensingmechanism, no successful clinical translation has hitherto beenmade. These protein-based materials are intolerant of long-term use and storage because of their denaturing and/or cytotoxic properties. We provide a solution by designing a protein-free and totally synthetic material-based approach. Capitalizing on the sugar-responsive properties of boronic acid, we have established a synthetic polymer gel-based insulin delivery device confined within a single catheter, which exhibits an artificial pancreas-like function in vivo. Subcutaneous implantation of the device in healthy and diabetic mice establishes a closed-loop systemcomposed of "continuous glucose sensing" and "skin layer"-regulated insulin release. As a result, glucose metabolism was controlled in response to interstitial glucose fluctuation under both insulin-deficient and insulin-resistant conditions with at least 3-week durability. Our "smart gel" technology could offer a user-friendly and remarkably economic (disposable) alternative to the current state of the art, thereby facilitating availability of effective insulin treatment not only to diabetic patients in developing countries but also to those patients who otherwise may not be strongly motivated, such as the elderly, infants, and patients in need of nursing care.

Original languageEnglish
Article numbereaaq0723
JournalScience Advances
Volume3
Issue number11
DOIs
Publication statusPublished - 2017 Nov
Externally publishedYes

ASJC Scopus subject areas

  • General

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