公益財団法人 セコム科学技術振興財団
研究成果報告書研究課題名

スマートインスリンデバイスによる革新的な糖尿病治療戦略の開発

Development of novel implantable artificial pancreas, a “smart” insulin device,for treatment of diabetes

研究期間
平成 28 年 10 月 ～ 令和 3 年 3 月

報告年月
令和 3 年 4 月
研究代表者
名古屋大学環境医学研究所 教授
菅波 孝祥
Nagoya University, Research Institute of Environmental Medicine, Professor
Takayoshi Suganami

1Abstract
Diabetes is a major global health threat that poses a devastating impact on society. Among a
growing lineup of medications for diabetes, insulin therapy continues to be a primary option inclinical practice for both palliative and preventive purposes. Indeed, a number of studies haveshown that tight glycemic control achieved with intensive insulin regimes can effectively reduce
the risk of developing or progressing the complications. Currently, the most common modality ofthis treatment is the patients’ self-administration, termed “open-loop” insulin delivery. However,this method inevitably suffers from inaccuracy of the dose control, where the overdose must be
strictly avoided otherwise causing acute and fatal hypoglycemia. Recently, a growing effort has
been focused on the development of a “closed-loop” or a self-regulated type of insulin delivery
system that is able to continuously deliver more accurate amount of insulin in response to thechange in blood glucose concentrations. These systems, so-called “artificial pancreas”, typicallycombine subcutaneously implanted glucose sensors and automated algorithm-driven insulin
infusing modules that are either electrically or wirelessly communicable. Whilst accumulating
reports validate this approach, limitations also persist. As for “electronics-derived” issues, theneed for frequent calibration and maintenance may impair ease of use and thus the users’ QOL.
In addition, these technologies may raise the therapeutic cost for diabetes.
In stark contrast to the above, our study focuses on a “protein-free”, totally synthetic approach,taking advantage of boronate-sugar binding chemistry. Boronic acid (BA) derivatives readily
complex with 1,2- and 1,3-cis-diols, including those present in glucose, through reversible
boronate ester formation. In this study, we showed that the boronate gel–based insulin-diffusion
control mechanism is weekly sustainable while also being acutely glucose-responsive on atimescale of tens of seconds, features potentially meeting the current unmet needs in insulin
therapy, including the management of glucose spikes. Thus, we created a catheter-combined
device scaled suitable for mouse experiments, which, upon subcutaneous implantation, could
control the glucose metabolism under both insulin-deficient and insulin-resistant conditions withat least 3-week durability. Then, we produced a hemodialysis (semipermeable) fiber-combined
device by installing a thin coat of the gel throughout the fiber surface but not within, thereby
achieving both a dramatically increased diffusion-active surface area (as compared to thepreviously reported catheter-combined type) and a smooth supply of insulin. And finally, wedeveloped a microneedle-combined device in order to dramatically reduce stress and invasion topatients. Our “smart-gel” technology could offer user-friendly and remarkably economic(disposable) alternative to the current state-of-the-art, thereby facilitating availability not only to3diabetic patients in developing countries, but also to those who otherwise may not be strongly
motivated such as the elderly, infants and patients in need of nursing care.

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