Evidence map›Paper›PMID 37813939›Full record

ArticleNature nanotechnology2024

Multivalent insulin receptor activation using insulin-DNA origami nanostructures.

Joel Spratt, José M Dias, Christina Kolonelou, Georges Kiriako, Enya Engström, Ekaterina Petrova, Christos Karampelias, Igor Cervenka, Natali Papanicolaou, Antonio Lentini and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Nature nanotechnology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
11.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 75 citations in OpenAlex.

  1. Review
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  11. Precise Regulation of Membrane Proteins: From Physical Technology to Biomolecular Strategy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
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  17. Bispecific DNA-Peptide Probes for Targeting Receptor Pairs on Live Cells.Angewandte Chemie (International ed. in English) · 2025
    Article
  18. Article
  19. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 1 institution in 2 countries.

Joel Spratt *Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
José M Dias *Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-1402-0323
Christina KolonelouDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-5625-5569
Georges KiriakoDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-6117-6286
Enya EngströmDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.ORCID 0009-0009-6574-0652
Ekaterina PetrovaDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Christos KarampeliasDepartment of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-9990-5760
Igor CervenkaDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Natali PapanicolaouDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-2931-3241
Antonio LentiniDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0003-1239-5495
Björn ReiniusDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-7021-5248
Olov AnderssonDepartment of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-6715-781X
Elena AmbrosettiDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Jorge L RuasDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Ana I TeixeiraDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. Ana.Teixeira@ki.se.ORCID 0000-0001-8169-8815
Karolinska Institutet · SE

Funding

Diabetesfonden (Stiftelsen Svenska Diabetesförbundets Forskningsfond) DIA2021-684EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)) ERC CoG 617711European Foundation for the Study of Diabetes (EFSD) NAKnut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation) KAW 2017.0114Novo Nordisk Fonden (Novo Nordisk Foundation) NNF19OC0057238Novo Nordisk Fonden (Novo Nordisk Foundation) NNF20OC0063993Novo Nordisk Fonden (Novo Nordisk Foundation) NNF22OC0075245Vetenskapsrådet (Swedish Research Council) 2016-00786Vetenskapsrådet (Swedish Research Council) 2020-01856Vetenskapsrådet (Swedish Research Council) 2022-02743
6 · The paper itself

Abstract

Insulin binds the insulin receptor (IR) and regulates anabolic processes in target tissues. Impaired IR signalling is associated with multiple diseases, including diabetes, cancer and neurodegenerative disorders. IRs have been reported to form nanoclusters at the cell membrane in several cell types, even in the absence of insulin binding. Here we exploit the nanoscale spatial organization of the IR to achieve controlled multivalent receptor activation. To control insulin nanoscale spatial organization and valency, we developed rod-like insulin-DNA origami nanostructures carrying different numbers of insulin molecules with defined spacings. Increasing the insulin valency per nanostructure markedly extended the residence time of insulin-DNA origami nanostructures at the receptors. Both insulin valency and spacing affected the levels of IR activation in adipocytes. Moreover, the multivalent insulin design associated with the highest levels of IR activation also induced insulin-mediated transcriptional responses more effectively than the corresponding monovalent insulin nanostructures. In an in vivo zebrafish model of diabetes, treatment with multivalent-but not monovalent-insulin nanostructures elicited a reduction in glucose levels. Our results show that the control of insulin multivalency and spatial organization with nanoscale precision modulates the IR responses, independent of the insulin concentration. Therefore, we propose insulin nanoscale organization as a design parameter in developing new insulin therapies.

Indexed as

DNANanostructuresReceptor, InsulinAnimalsDiabetes MellitusInsulinZebrafishDNAInsulinReceptor, Insulin

Identifiers

PMID37813939
PMCPMC10873203
OpenAlexW4387451501

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.