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Unconventional insulins from predators and pathogens

Abstract

Insulin and its related peptides are found throughout the animal kingdom, in which they serve diverse functions. This includes regulation of glucose homeostasis, neuronal development and cognition. The surprising recent discovery that venomous snails evolved specialized insulins to capture fish demonstrated the nefarious use of this hormone in nature. Because of their streamlined role in predation, these repurposed insulins exhibit unique characteristics that have unraveled new aspects of the chemical ecology and structural biology of this important hormone. Recently, insulins were also reported in other venomous predators and pathogenic viruses, demonstrating the broader use of insulin by one organism to manipulate the physiology of another. In this Review, we provide an overview of the discovery and biomedical application of repurposed insulins and other hormones found in nature and highlight several unique insights gained from these unusual compounds.

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Fig. 1: The fish-hunting cone snail C. geographus uses insulin for prey capture.
Fig. 2: Insights gained from cone snail insulins and their analogs based on structural studies.
Fig. 3: Diversity of insulin sequences identified in the venom glands of cone snails and other members of the superfamily Conoidea.
Fig. 4: Viral insulin-like sequences (VILPs) share high sequence and structural similarity with members of the human insulin superfamily.

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Acknowledgements

We thank T. Lund Koch for assistance with structural predictions of VILPs and sequence analysis of venom insulins, P. Flórez Salcedo for illustrations used in the graphical abstract and Y.W. Zhang for helpful discussion of viral insulin sequences. H.S.-H. and S.H.L. receive support from the Carlsberg Foundation (CF19-0445). D.H.-C.C. receives support from National Institute of Health (DK120430).

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Correspondence to Helena Safavi-Hemami.

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D.H.-C.C. and H.S.-H. hold patents on the insulin analogs mini-Ins G1 and Vh-Ins-HSLQ.

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Nature Chemical Biology thanks Emrah Altindis and Alexander Zaykov for their contribution to the peer review of this work.

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Laugesen, S.H., Chou, D.HC. & Safavi-Hemami, H. Unconventional insulins from predators and pathogens. Nat Chem Biol 18, 688–697 (2022). https://doi.org/10.1038/s41589-022-01068-6

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