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Issue 11, 2019

A forskolin-conjugated insulin analog targeting endogenous glucose-transporter for glucose-responsive insulin delivery

Author affiliations

Abstract

Insulin administration for the management of diabetes is accompanied by hypoglycemia, which is expected to be mitigated by glucose-responsive smart insulin that has self-regulation ability in response to blood glucose level (BGL) fluctuation. Here, we have prepared a new insulin analog by modifying insulin with forskolin (designated as insulin-F), a glucose-transporter (Glut) inhibitor. In vitro, insulin-F is capable of binding to Glut on erythrocyte ghosts, which can be inhibited by glucose and cytochalasin B. Upon subcutaneous injection in type 1 diabetic mice, insulin-F maintains BGLs below 200 mg mL−1 for up to 10 h, and achieves 20 h with two sequential injections. Moreover, insulin-F also binds to endogenous Gluts. Upon a glucose challenge, the elevated level of glucose competitively replaces and liberates insulin-F that binds to Glut, rapidly restoring BGLs to the normal range.

Graphical abstract: A forskolin-conjugated insulin analog targeting endogenous glucose-transporter for glucose-responsive insulin delivery

Supplementary files

Article information


Submitted
14 Aug 2019
Accepted
18 Sep 2019
First published
14 Oct 2019

Biomater. Sci., 2019,7, 4508-4513
Article type
Communication

A forskolin-conjugated insulin analog targeting endogenous glucose-transporter for glucose-responsive insulin delivery

J. Wang, Z. Wang, J. Yu, Y. Zhang, Y. Zeng and Z. Gu, Biomater. Sci., 2019, 7, 4508 DOI: 10.1039/C9BM01283D

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