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Week-long Norm Glycaemia in Diabetic Mice and Minipigs via a Subcutaneous Dose of a Glucose-responsive Insulin Complex by Juan Zhang; Xiangqian Wei; Wei Liu; Yanfang Wang; Anna R. Kahkoska; Xianchi Zhou; Huimin Zheng; Wentao Zhang; Tao Sheng; Yang Zhang; Yun Liu; Kangfan Ji; Yichen Xu; Peng Zhang; Jianchang Xu; John. B. Buse; Jinqiang Wang; Zhen Gu is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Week-long Norm Glycaemia in Diabetic Mice and Minipigs via a Subcutaneous Dose of a Glucose-responsive Insulin Complex about?

Glucose-responsive formulations of insulin can increase its therapeutic index and reduce the burden of its administration. However, it has been difficult to develop single-dosage formulations that can release insulin in both a sustained and glucose-responsive manner. Here we report the development of a subcutaneously injected glucose-responsive formulation that nearly does not trigger the formation of a fibrous capsule and that leads to week-long normoglycaemia and negligible hypoglycaemia in mice and minipigs with type 1 diabetes. The formulation consists of gluconic acid-modified recombinant human insulin binding tightly to poly-l-lysine modified by 4-carboxy-3-fluorophenylboronic acid via glucose-responsive phenylboronic acid-diol complexation and electrostatic attraction. When the insulin complex is exposed to high glucose concentrations, the phenylboronic acid moieties of the polymers bind rapidly to glucose, breaking the complexation and reducing the polymers' positive charge density, which promotes the release of insulin. The therapeutic performance of this long-acting single-dose formulation supports its further evaluation and clinical translational studies. Diabetes mellit

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Author

Juan Zhang; Xiangqian Wei; Wei Liu; Yanfang Wang; Anna R. Kahkoska; Xianchi Zhou; Huimin Zheng; Wentao Zhang; Tao Sheng; Yang Zhang; Yun Liu; Kangfan Ji; Yichen Xu; Peng Zhang; Jianchang Xu; John. B. Buse; Jinqiang Wang; Zhen Gu

Publisher

Springer Science and Business Media LLC

Published

2023

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)