ArticleNature communications2022
Functionally selective signaling and broad metabolic benefits by novel insulin receptor partial agonists.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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
18 citing papers in PubMed, 28 citations in OpenAlex.
- Structural basis of insulin receptor antagonism by bivalent site 1-site 2 ligands S961 and Ins-AC-S2.Nature communications · 2026Article
- Single-position ligand modifications tune CBChemical science · 2026Article
- Structural mechanism of insulin receptor activation by a dimeric aptamer agonist.Experimental & molecular medicine · 2025Article
- Elucidation of Mechanism of Action in Drug Invention: Using Stable Isotope Tracers to Unravel Biochemical Kinetics.Pharmacology research & perspectives · 2025Review
- Design of a novel long-acting insulin analogs by acetylation modification and compared with insulin Icodec.Scientific reports · 2025Article
- Spontaneous Dimerization and Distinct Packing Modes of Transmembrane Domains in Receptor Tyrosine Kinases.Biochemistry · 2024Article
- Spontaneous Dimerization and Distinct Packing Modes of Transmembrane Domains in Receptor Tyrosine Kinases.bioRxiv : the preprint server for biology · 2024Article
- Di-PEGylated insulin: A long-acting insulin conjugate with superior safety in reducing hypoglycemic events.Acta pharmaceutica Sinica. B · 2024Article
- Multivalent insulin receptor activation using insulin-DNA origami nanostructures.Nature nanotechnology · 2024Article
- Insulin signaling in development.Development (Cambridge, England) · 2023Article
- How Neuromembrane Lipids Modulate Membrane Proteins: Insights from G-Protein-Coupled Receptors (GPCRs) and Receptor Tyrosine Kinases (RTKs).Cold Spring Harbor perspectives in biology · 2023Review
- A stepwise activation model for the insulin receptor.Experimental & molecular medicine · 2023Review
- Non-Native Site-Selective Enzyme Catalysis.Chemical reviews · 2023Review
- Discovery and multimerization of cross-reactive single-domain antibodies against SARS-like viruses to enhance potency and address emerging SARS-CoV-2 variants.Scientific reports · 2023Article
- Modulation of the antagonistic properties of an insulin mimetic peptide by disulfide bridge modifications.Journal of peptide science : an official publication of the European Peptide Society · 2023Article
- Recombinant Insulin-Like Growth Factor 1 Dimers: Receptor Binding Affinities and Activation Abilities.International journal of peptide research and therapeutics · 2023Article
- Functional selectivity of insulin receptor revealed by aptamer-trapped receptor structures.Nature communications · 2022Article
- Discovery of Insulin/GLP-1/Glucagon Triagonists for the Treatment of Diabetes and Obesity.ACS medicinal chemistry letters · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
25 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Insulin analogs have been developed to treat diabetes with focus primarily on improving the time action profile without affecting ligand-receptor interaction or functional selectivity. As a result, inherent liabilities (e.g. hypoglycemia) of injectable insulin continue to limit the true therapeutic potential of related agents. Insulin dimers were synthesized to investigate whether partial agonism of the insulin receptor (IR) tyrosine kinase is achievable, and to explore the potential for tissue-selective systemic insulin pharmacology. The insulin dimers induced distinct IR conformational changes compared to native monomeric insulin and substrate phosphorylation assays demonstrated partial agonism. Structurally distinct dimers with differences in conjugation sites and linkers were prepared to deliver desirable IR partial agonist (IRPA). Systemic infusions of a B29-B29 dimer in vivo revealed sharp differences compared to native insulin. Suppression of hepatic glucose production and lipolysis were like that attained with regular insulin, albeit with a distinctly shallower dose-response. In contrast, there was highly attenuated stimulation of glucose uptake into muscle. Mechanistic studies indicated that IRPAs exploit tissue differences in receptor density and have additional distinctions pertaining to drug clearance and distribution. The hepato-adipose selective action of IRPAs is a potentially safer approach for treatment of diabetes.
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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.