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Fish-hunting cone snail disrupts prey’s glucose homeostasis with weaponized mimetics of somatostatin and insulin

Author

Listed:
  • Ho Yan Yeung

    (University of Copenhagen
    University of Utah)

  • Iris Bea L. Ramiro

    (University of Copenhagen)

  • Daniel B. Andersen

    (University of Copenhagen
    Novo Nordisk Foundation Centre for Basic Metabolic Research)

  • Thomas Lund Koch

    (University of Copenhagen
    University of Utah
    University of Utah)

  • Alexander Hamilton

    (University of Copenhagen
    Lund University)

  • Walden E. Bjørn-Yoshimoto

    (University of Copenhagen)

  • Samuel Espino

    (University of Utah)

  • Sergey Y. Vakhrushev

    (University of Copenhagen)

  • Kasper B. Pedersen

    (University of Copenhagen)

  • Noortje Haan

    (Center for Proteomics and Metabolomics)

  • Agnes L. Hipgrave Ederveen

    (Center for Proteomics and Metabolomics)

  • Baldomero M. Olivera

    (University of Utah)

  • Jakob G. Knudsen

    (University of Copenhagen)

  • Hans Bräuner-Osborne

    (University of Copenhagen)

  • Katrine T. Schjoldager

    (University of Copenhagen)

  • Jens Juul Holst

    (University of Copenhagen
    Novo Nordisk Foundation Centre for Basic Metabolic Research)

  • Helena Safavi-Hemami

    (University of Copenhagen
    University of Utah
    University of Utah)

Abstract

Venomous animals have evolved diverse molecular mechanisms to incapacitate prey and defend against predators. Most venom components disrupt nervous, locomotor, and cardiovascular systems or cause tissue damage. The discovery that certain fish-hunting cone snails use weaponized insulins to induce hypoglycemic shock in prey highlights a unique example of toxins targeting glucose homeostasis. Here, we show that, in addition to insulins, the deadly fish hunter, Conus geographus, uses a selective somatostatin receptor 2 (SSTR2) agonist that blocks the release of the insulin-counteracting hormone glucagon, thereby exacerbating insulin-induced hypoglycemia in prey. The native toxin, Consomatin nG1, exists in several proteoforms with a minimized vertebrate somatostatin-like core motif connected to a heavily glycosylated N-terminal region. We demonstrate that the toxin’s N-terminal tail closely mimics a glycosylated somatostatin from fish pancreas and is crucial for activating the fish SSTR2. Collectively, these findings provide a stunning example of chemical mimicry, highlight the combinatorial nature of venom components, and establish glucose homeostasis as an effective target for prey capture.

Suggested Citation

  • Ho Yan Yeung & Iris Bea L. Ramiro & Daniel B. Andersen & Thomas Lund Koch & Alexander Hamilton & Walden E. Bjørn-Yoshimoto & Samuel Espino & Sergey Y. Vakhrushev & Kasper B. Pedersen & Noortje Haan & , 2024. "Fish-hunting cone snail disrupts prey’s glucose homeostasis with weaponized mimetics of somatostatin and insulin," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50470-2
    DOI: 10.1038/s41467-024-50470-2
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    1. Francois Moreau & Nicholas S. Kirk & Fa Zhang & Vasily Gelfanov & Edward O. List & Martina Chrudinová & Hari Venugopal & Michael C. Lawrence & Veronica Jimenez & Fatima Bosch & John J. Kopchick & Rich, 2022. "Interaction of a viral insulin-like peptide with the IGF-1 receptor produces a natural antagonist," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Thomas D. Madsen & Lasse H. Hansen & John Hintze & Zilu Ye & Shifa Jebari & Daniel B. Andersen & Hiren J. Joshi & Tongzhong Ju & Jens P. Goetze & Cesar Martin & Mette M. Rosenkilde & Jens J. Holst & R, 2020. "An atlas of O-linked glycosylation on peptide hormones reveals diverse biological roles," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
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