Fish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor
The fish-hunting marine cone snail Conus geographus uses a specialized venom insulin to induce hypoglycemic shock in its prey. We recently showed that this venom insulin, Con-Ins G1, has unique characteristics relevant to the design of new insulin therapeutics. Here, we show that fish-hunting cone s...
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eLife Sciences Publications Ltd
2019
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oai:doaj.org-article:71443f02920a4c85a8dd87031b11da692021-11-09T16:12:26ZFish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor10.7554/eLife.415742050-084Xe41574https://doaj.org/article/71443f02920a4c85a8dd87031b11da692019-02-01T00:00:00Zhttps://elifesciences.org/articles/41574https://doaj.org/toc/2050-084XThe fish-hunting marine cone snail Conus geographus uses a specialized venom insulin to induce hypoglycemic shock in its prey. We recently showed that this venom insulin, Con-Ins G1, has unique characteristics relevant to the design of new insulin therapeutics. Here, we show that fish-hunting cone snails provide a rich source of minimized ligands of the vertebrate insulin receptor. Insulins from C. geographus, Conus tulipa and Conus kinoshitai exhibit diverse sequences, yet all bind to and activate the human insulin receptor. Molecular dynamics reveal unique modes of action that are distinct from any other insulins known in nature. When tested in zebrafish and mice, venom insulins significantly lower blood glucose in the streptozotocin-induced model of diabetes. Our findings suggest that cone snails have evolved diverse strategies to activate the vertebrate insulin receptor and provide unique insight into the design of novel drugs for the treatment of diabetes.Peter AhorukomeyeMaria M DisotuarJoanna GajewiakSanthosh KaranthMaren WatkinsSamuel D RobinsonPaula Flórez SalcedoNicholas A SmithBrian J SmithAmnon SchlegelBriony E ForbesBaldomero OliveraDanny Hung-Chieh ChouHelena Safavi-HemamieLife Sciences Publications Ltdarticlecone snailvenominsulinhypoglycemic shockprey capturediabetesMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 8 (2019) |
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cone snail venom insulin hypoglycemic shock prey capture diabetes Medicine R Science Q Biology (General) QH301-705.5 |
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cone snail venom insulin hypoglycemic shock prey capture diabetes Medicine R Science Q Biology (General) QH301-705.5 Peter Ahorukomeye Maria M Disotuar Joanna Gajewiak Santhosh Karanth Maren Watkins Samuel D Robinson Paula Flórez Salcedo Nicholas A Smith Brian J Smith Amnon Schlegel Briony E Forbes Baldomero Olivera Danny Hung-Chieh Chou Helena Safavi-Hemami Fish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor |
| description |
The fish-hunting marine cone snail Conus geographus uses a specialized venom insulin to induce hypoglycemic shock in its prey. We recently showed that this venom insulin, Con-Ins G1, has unique characteristics relevant to the design of new insulin therapeutics. Here, we show that fish-hunting cone snails provide a rich source of minimized ligands of the vertebrate insulin receptor. Insulins from C. geographus, Conus tulipa and Conus kinoshitai exhibit diverse sequences, yet all bind to and activate the human insulin receptor. Molecular dynamics reveal unique modes of action that are distinct from any other insulins known in nature. When tested in zebrafish and mice, venom insulins significantly lower blood glucose in the streptozotocin-induced model of diabetes. Our findings suggest that cone snails have evolved diverse strategies to activate the vertebrate insulin receptor and provide unique insight into the design of novel drugs for the treatment of diabetes. |
| format |
article |
| author |
Peter Ahorukomeye Maria M Disotuar Joanna Gajewiak Santhosh Karanth Maren Watkins Samuel D Robinson Paula Flórez Salcedo Nicholas A Smith Brian J Smith Amnon Schlegel Briony E Forbes Baldomero Olivera Danny Hung-Chieh Chou Helena Safavi-Hemami |
| author_facet |
Peter Ahorukomeye Maria M Disotuar Joanna Gajewiak Santhosh Karanth Maren Watkins Samuel D Robinson Paula Flórez Salcedo Nicholas A Smith Brian J Smith Amnon Schlegel Briony E Forbes Baldomero Olivera Danny Hung-Chieh Chou Helena Safavi-Hemami |
| author_sort |
Peter Ahorukomeye |
| title |
Fish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor |
| title_short |
Fish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor |
| title_full |
Fish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor |
| title_fullStr |
Fish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor |
| title_full_unstemmed |
Fish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor |
| title_sort |
fish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor |
| publisher |
eLife Sciences Publications Ltd |
| publishDate |
2019 |
| url |
https://doaj.org/article/71443f02920a4c85a8dd87031b11da69 |
| work_keys_str_mv |
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