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Engineering synthetically modified insulin for glucose-responsive diabetes therapy

Author(s)
Webber, Matthew; Anderson, Daniel Griffith; Langer, Robert S
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Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/
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Abstract
Though a suite of different insulin variants have been used clinically to provide greater control over pharmacokinetics, no clinically used insulin can tune its potency and/or bioavailability in a glucose-dependent manner. In order to improve therapy for diabetic patients, a vision has been the development of autonomous closed-loop approaches. Toward this goal, insulin has been synthetically modified with glucose-sensing groups or groups that can compete with free glucose for binding to glucose-binding proteins and evaluated in pre-clinical models. Specifically, it was demonstrated that site-specific modification of insulin with phenylboronic acid can result in glucose-responsive activity, leading to faster recovery in diabetic mice following a glucose challenge but with less observed hypoglycemia in healthy mice. This strategy, along with several others being pursued, holds promise to improve the fidelity in glycemic control with routine insulin therapy. Keywords: bioartificial pancreas; bionic pancreas; concanavalin A; diabetes; drug delivery; fully synthetic pancreas; lectin; phenylboronic acid
Date issued
2015-07
URI
https://hdl.handle.net/1721.1/122011
Department
Massachusetts Institute of Technology. Department of Chemical Engineering; Massachusetts Institute of Technology. Institute for Medical Engineering & Science; Harvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Biological Engineering; Koch Institute for Integrative Cancer Research at MIT
Journal
Expert Review of Endocrinology & Metabolism
Publisher
Informa UK Limited
Citation
Webber, Matthew J. et al. "Engineering synthetically modified insulin for glucose-responsive diabetes therapy." Expert Review of Endocrinology & Metabolism 10, 5 (July 2015): 483-489 © 2015 Informa UK, Ltd
Version: Author's final manuscript
ISSN
1744-6651
1744-8417

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