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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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).
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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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