Engineering synthetically modified insulin for glucose-responsive diabetes therapy
Name
nihms774984.pdf
Description
Accepted version
Size
464.75 KB
Format
Adobe PDF
Checksum (MD5)
f2fea4f1ebd5174c8a5d68e1b85d00b5
Author(s)
Webber, Matthew
Anderson, Daniel Griffith
Langer, Robert S
Date Issued
July 2015
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
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
MIT 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
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1586/17446651.2015.1071187
