ArticleNature2013
How insulin engages its primary binding site on the insulin receptor.
Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 194 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
194 citing papers in PubMed, 2 syntheses or guidelines pooled it, 424 citations in OpenAlex.
- Pooled it
- Correlations Between Abnormal Glucose Metabolism and Bone Mineral Density or Bone Metabolism.Medical science monitor : international medical journal of experimental and clinical research · 2016Pooled it
- Insulin mimetics and non-canonical insulin receptor signaling: mechanisms and disease relevance.Experimental & molecular medicine · 2026Review
- Insulin resistance in the 21st century: new takes on an old problem-2025 Diabetes, Diabetes Care, and Diabetologia Expert Forum.Diabetologia · 2026Review
- Monomeric Insulin Analog and Stabilizing Excipient Enabled Ultrafast Insulin Formulation.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Damping amyloid-associated conformational fluctuations in a protein by an engineered diselenide bridge.Protein science : a publication of the Protein Society · 2026Article
- Diagnostic utility of fasting versus non-fasting blood glucose: contextualising testing strategies-a narrative review.Diabetology & metabolic syndrome · 2026Review
- Structural basis of insulin receptor antagonism by bivalent site 1-site 2 ligands S961 and Ins-AC-S2.Nature communications · 2026Article
- Nematode extracellular protein interactome expands connections between signaling pathways.Cell genomics · 2026Article
- Reprogramming insulin receptor activation with a de novo agonist to overcome severe insulin resistance.bioRxiv : the preprint server for biology · 2026Article
- Direct Selection of Functional De Novo Macrocycles for Activation of On-Cellulo Insulin Receptor.Angewandte Chemie (International ed. in English) · 2026Article
- Evolution of Insulin, Insulin-like Growth Factors, and Their Cognate Receptors in Vertebrates, Invertebrates, and Viruses.Molecular biology and evolution · 2026Article
- Deep mutational scanning of the human insulin receptor ectodomain to inform precision therapy for insulin resistance.Nature communications · 2025Article
- Characterization of S-homocysteinylation of Human Insulin and Its Implications in Diabetes.The protein journal · 2025Article
- Insulin facilitates entry of calcium ions into human and murine erythrocytes via Piezo1: a newly identified mechanism with implications for type 2 diabetes.The FEBS journal · 2025Article
- Emerging Insulin Analogues: A Glimpse into How Insulin Analogues May Look in the near Future.Pharmaceutics · 2025Review
- Ultrastable Insulin-Glucagon Fusion Protein Exploits an Endogenous Hepatic Switch to Mitigate Hypoglycemic Risk.ACS pharmacology & translational science · 2025Article
- Nidulin stimulates glucose uptake in myotubes through the IRS-AKT pathway and alters redox balance and intracellular calcium.Natural products and bioprospecting · 2025Article
- Structural mechanism of insulin receptor activation by a dimeric aptamer agonist.Experimental & molecular medicine · 2025Article
- Regulation and function of insulin and insulin-like growth factor receptor signalling.Nature reviews. Molecular cell biology · 2025Review
134 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 4 countries.
Funding
Abstract
Insulin receptor signalling has a central role in mammalian biology, regulating cellular metabolism, growth, division, differentiation and survival. Insulin resistance contributes to the pathogenesis of type 2 diabetes mellitus and the onset of Alzheimer's disease; aberrant signalling occurs in diverse cancers, exacerbated by cross-talk with the homologous type 1 insulin-like growth factor receptor (IGF1R). Despite more than three decades of investigation, the three-dimensional structure of the insulin-insulin receptor complex has proved elusive, confounded by the complexity of producing the receptor protein. Here we present the first view, to our knowledge, of the interaction of insulin with its primary binding site on the insulin receptor, on the basis of four crystal structures of insulin bound to truncated insulin receptor constructs. The direct interaction of insulin with the first leucine-rich-repeat domain (L1) of insulin receptor is seen to be sparse, the hormone instead engaging the insulin receptor carboxy-terminal α-chain (αCT) segment, which is itself remodelled on the face of L1 upon insulin binding. Contact between insulin and L1 is restricted to insulin B-chain residues. The αCT segment displaces the B-chain C-terminal β-strand away from the hormone core, revealing the mechanism of a long-proposed conformational switch in insulin upon receptor engagement. This mode of hormone-receptor recognition is novel within the broader family of receptor tyrosine kinases. We support these findings by photo-crosslinking data that place the suggested interactions into the context of the holoreceptor and by isothermal titration calorimetry data that dissect the hormone-insulin receptor interface. Together, our findings provide an explanation for a wealth of biochemical data from the insulin receptor and IGF1R systems relevant to the design of therapeutic insulin analogues.
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What OpenQuestion holds
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.