ArticleScience advances2023
Structural basis of insulin fibrillation.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- Characterization of the pH-Dependent Stabilizing Forces of Insulin's Native and Fibril States.ACS physical chemistry Au · 2026Article
- Buccal Insulin Delivery Systems: Formulation Approaches, Stability Constraints, and Translational Prospects.Pharmaceutics · 2026Review
- Damping amyloid-associated conformational fluctuations in a protein by an engineered diselenide bridge.Protein science : a publication of the Protein Society · 2026Article
- Physicochemical Stability of Insulin and Analogues in Saline Infusion: Screening for Amyloid and Amorphous High-Molecular-Weight Material.ACS omega · 2026Article
- Towards the development of an insulin degradation test.bioRxiv : the preprint server for biology · 2026Article
- Towards the Development of an Insulin Degradation Test.Journal of diabetes research · 2026Article
- Disassembly of chiral hydrogen-bonded frameworks into single-unit organometallic helices for enantioselective amyloid inhibition.Nature communications · 2025Article
- 2-Styrylquinolines with Push-Pull Architectures as Sensors for β-Amyloid Aggregation with Theranostic Properties.International journal of molecular sciences · 2025Article
- Spatially constrained disulfide bond shuffling delays insulin aggregation and enhances neurotoxicity.Nature communications · 2025Article
- Anionic Lipid Catalyzes the Generation of Cytotoxic Insulin Oligomers.Biomolecules · 2025Article
- Regulation and function of insulin and insulin-like growth factor receptor signalling.Nature reviews. Molecular cell biology · 2025Review
- The evolving role of solid state nuclear magnetic resonance methods in studies of amyloid fibrils.Current opinion in structural biology · 2025Review
- Stabilization of a protein by a single halogen-based aromatic amplifier.Protein science : a publication of the Protein Society · 2025Article
- Structural insights into the role of reduced cysteine residues in SOD1 amyloid filament formation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Site-Specific Glyco-Tagging of Native Proteins for the Development of Biologicals.Journal of the American Chemical Society · 2024Article
- Atomic resolution structure of full-length human insulin fibrils.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Activation of the insulin receptor by insulin-like growth factor 2.Nature communications · 2024Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Insulin is a hormone responsible for maintaining normal glucose levels by activating insulin receptor (IR) and is the primary treatment for diabetes. However, insulin is prone to unfolding and forming cross-β fibers. Fibrillation complicates insulin storage and therapeutic application. Molecular details of insulin fibrillation remain unclear, hindering efforts to prevent fibrillation process. Here, we characterized insulin fibrils using cryo-electron microscopy (cryo-EM), showing multiple forms that contain one or more of the protofilaments containing both the A and B chains of insulin linked by disulfide bonds. We solved the cryo-EM structure of one of the fibril forms composed of two protofilaments at 3.2-Å resolution, which reveals both the β sheet conformation of the protofilament and the packing interaction between them that underlie the fibrillation. On the basis of this structure, we designed several insulin mutants that display reduced fibrillation while maintaining native IR signaling activity. These designed insulin analogs may be developed into more effective therapeutics for type 1 diabetes.
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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 Socratic graph.