ArticleProceedings of the National Academy of Sciences of the United States of America2019
Glucose transporter inhibitor-conjugated insulin mitigates hypoglycemia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 56 citations in OpenAlex.
- Targeting GLUTs in Cancer: Mechanisms, Combination Strategies, and Translational Challenges.Current medical science · 2026Review
- Review
- Mechanistic Role of Disulfidptosis in Type 2 Diabetes Mellitus.Molecular nutrition & food research · 2026Review
- [Advances in injectable and transdermal glucose-responsive insulin delivery systems].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Review
- Ultrastable Insulin-Glucagon Fusion Protein Exploits an Endogenous Hepatic Switch to Mitigate Hypoglycemic Risk.ACS pharmacology & translational science · 2025Article
- Molecular basis of SLC19A1-mediated folate and cyclic dinucleotide transport.Nature communications · 2025Article
- An orally administered glucose-responsive polymeric complex for high-efficiency and safe delivery of insulin in mice and pigs.Nature nanotechnology · 2024Article
- Cell-drug conjugates.Nature biomedical engineering · 2024Review
- Research hotspots and trends in diabetes and insulin resistance: a bibliometric analysis.Frontiers in nutrition · 2024Article
- In Silico Investigation of the Clinical Translatability of Competitive Clearance Glucose-Responsive Insulins.ACS pharmacology & translational science · 2023Article
- Rational Design and Efficacy of Glucose-Responsive Insulin Therapeutics and Insulin Delivery Systems by Computation Using Connected Human and Rodent Models.Advanced healthcare materials · 2023Article
- Neuronal AR Regulates Glucose Homeostasis and Energy Expenditure in Lean Female Mice With Androgen Excess.Endocrinology · 2023Article
- Material design for oral insulin delivery.Med-X · 2023Review
- Insulin: evolution of insulin formulations and their application in clinical practice over 100 years.Acta diabetologica · 2022Review
- Molecular basis for inhibiting human glucose transporters by exofacial inhibitors.Nature communications · 2022Article
- New Horizons: Next-Generation Insulin Analogues: Structural Principles and Clinical Goals.The Journal of clinical endocrinology and metabolism · 2022Review
- Recent Advances of Microneedles and Their Application in Disease Treatment.International journal of molecular sciences · 2022Review
- Innovations in Disease State Responsive Soft Materials for Targeting Extracellular Stimuli Associated with Cancer, Cardiovascular Disease, Diabetes, and Beyond.Advanced materials (Deerfield Beach, Fla.) · 2021Review
- Structural principles of insulin formulation and analog design: A century of innovation.Molecular metabolism · 2021Review
- 'Smart' insulin-delivery technologies and intrinsic glucose-responsive insulin analogues.Diabetologia · 2021Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
Insulin therapy in the setting of type 1 and advanced type 2 diabetes is complicated by increased risk of hypoglycemia. This potentially fatal complication could be mitigated by a glucose-responsive insulin analog. We report an insulin-facilitated glucose transporter (Glut) inhibitor conjugate, in which the insulin molecule is rendered glucose-responsive via conjugation to an inhibitor of Glut. The binding affinity of this insulin analog to endogenous Glut is modulated by plasma and tissue glucose levels. In hyperglycemic conditions (e.g., uncontrolled diabetes or the postprandial state), the in situ-generated insulin analog-Glut complex is driven to dissociate, freeing the insulin analog and glucose-accessible Glut to restore normoglycemia. Upon overdose, enhanced binding of insulin analog to Glut suppresses the glucose transport activity of Glut to attenuate further uptake of glucose. We demonstrate the ability of this insulin conjugate to regulate blood glucose levels within a normal range while mitigating the risk of hypoglycemia in a type 1 diabetic mouse model.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.