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Cited by 5Diabetes Management and ResearchAdvanced Drug Delivery SystemsHydrogels: synthesis, properties, applications

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Long-acting glucose-responsive insulin with swift onset-of-action

Liu, Wei, Zhang, Juan, Wang, Yanfang, He, Yaqin, Wang, Yuanwu, Wei, Xiangqian, Yao, Yuejun, Xu, Jianchang, Zhang, Wentao, Sheng, Tao, Dai, Haibin, Wang, Jinqiang, Gu, Zhen·2025·Journal of Controlled Release
DOI 10.1016/j.jconrel.2025.113826
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Abstract

Long-acting glucose-responsive insulin is anticipated to reduce the frequency of injections via replacing both rapid-acting and long-acting insulin. Sequential rapid glucose-responsive insulin release and instant absorption are essential to the swift onset of action. Herein, we have developed injectable long-acting glucose-responsive insulin formulations (GRIF) prepared from glucosamine-modified insulin aspart (ASP-G n ) and phenylboronic acid-modified poly-ʟ-lysine (PLL-FPBA). The complex can form stable GRIF reservoir subcutaneously after injection. Upon food intake, the elevated blood glucose (BG) triggers the release of monomolecular insulin aspart (or ASP-G n ), which can be absorbed immediately to downregulate BG back to the normal range. Among the diverse formulations investigated, GRIF prepared from two-glucosamine-modified insulin aspart and twice weight of PLL-FPBA facilitates the best in vitro glucose-responsive insulin release performance. In type 1 diabetic mouse and minipig models, GRIF exhibit notably swift onset of action and achieve superior BG control. In addition, GRIF reveal no discernible signs of associated toxicity in the studied animals.

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  • Glucose-responsive insulins (GRIs) and controlled-release insulin analogues aim to decouple metabolic efficacy from rigid injection timing, modulating insulin activity in response to ambient glucose levels.

    “In this context, glucose-responsive insulins (GRIs) and controlled-release insulin analogues aim to decouple metabolic efficacy from rigid injection timing, modulating insulin activity in response to ambient glucose levels:”

    From Diabetic gastroparesis: pathophysiology and impact on insulin timing choices (2026) · cites this paper as [164]

  • GRIs are designed to increase their activity or release rate during hyperglycemia and to reduce activity during normoglycemia or impending hypoglycemia.

    “GRIs are designed to increase their activity or release rate during hyperglycemia and to reduce activity during normoglycemia or impending hypoglycemia [162–164].”

    From Diabetic gastroparesis: pathophysiology and impact on insulin timing choices (2026) · cites this paper as [164]

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Metadata

Authors
Liu, W., Zhang, J., Wang, Y., He, Y., Wang, Y., Wei, X., Yao, Y., Xu, J., Zhang, W., Sheng, T., Dai, H., Wang, J., & Gu, Z.
Affiliations
  • Zhejiang University (CN)
  • Second Affiliated Hospital of Zhejiang University (CN)
  • Sir Run Run Shaw Hospital (CN)
Corresponding author
  • Dai, Haibin
  • Wang, Jinqiang
  • Gu, Zhen
ORCID
Venue
Journal of Controlled Release
Publisher
Elsevier BV
Published
2025-07
Volume
383
Pages
113826
ISSN
0168-3659 (ISSN-L)
DOI
10.1016/j.jconrel.2025.113826
OpenAlex
W4410194952
Cited by
5
References
45
Citations by year
2026: 5
FWCI
3.41
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Journal of Controlled Release (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Key Research and Development Program of China (2022YFE0202200)
  • Key Research and Development Program of Zhejiang Province (2024C03085)
  • Department of Surgery
  • Zhejiang University
  • National Natural Science Foundation of China (32471374)
  • Breakthrough T1D (2-SRA-2021-1064-M-B, 2-SRA-2022-1159-M-B)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
Keywords
glucose-responsive insulin, long-acting insulin, insulin aspart, phenylboronic acid, poly-L-lysine, glycemic control, type 1 diabetes
MeSH terms
Animals, Blood Glucose, Boronic Acids, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 1, Glucosamine, Hypoglycemic Agents, Male, Polylysine, Swine, Swine, Miniature, Insulin, Long-Acting, Mice, Insulin Aspart, Drug Liberation

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