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Updated: Jan 14, 2026

Glucose-Stimulated Insulin Secretion via Perfusion through the Mice Vasculature with an Intact Pancreas
Published on: July 25, 2025
Poly(bis(guanidinium)-oxazoline)-Insulin Complex Exerting Long-Acting Glucose-Responsive Insulin Release in Mice and
Haodong Zhang1, Qian Liang2, Weinan Jiang3
1State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
Abstract:
Glucose-responsive insulin formulations, utilizing electrostatic interactions between positively charged polymers and negatively charged insulin, offer significant potential to enhance the therapeutic index of insulin while alleviating the burden of frequent administration. However, their clinical application is limited by concerns on the uncontrolled insulin release, including the dangerous hypoglycemic events. Here, we develop a glucose-responsive insulin formulation for subcutaneous administration, which exhibits exceptional biocompatibility and maintains normoglycemia over 192 h in type 1 diabetic minipigs after a single dose, with negligible hypoglycemia. The formulation comprises recombinant human insulin, tightly binding to bis(guanidinium)-functionalized poly(2-oxazoline) polymers, which are further modified with phenylboronic acid to enable glucose responsive insulin release. Bis-guanidinium strengthens the electrostatic interaction with insulin, thereby preventing uncontrolled insulin release and prolonging the therapeutic effect in vivo. This bis(guanidinium)-functionalized polymer strategy opens new avenues for developing glucose-responsive insulin formulations.
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