Fish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor
| Autor: | Maria M. Disotuar, Brian J. Smith, Samuel D. Robinson, Paula Flórez Salcedo, Danny Hung-Chieh Chou, Peter Ahorukomeye, Nicholas A. Smith, Baldomero M. Olivera, Santhosh Karanth, Amnon Schlegel, Briony E. Forbes, Maren Watkins, Joanna Gajewiak, Helena Safavi-Hemami |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
genetic structures medicine.medical_treatment receptors venom Venom Poisons Mice 0302 clinical medicine Biology (General) Receptor Zebrafish cone snail biology diabetes General Neuroscience Conus tulipa Poisoning General Medicine prey capture Cell biology Medicine Insight insulin QH301-705.5 hypoglycemic shock Science Mollusk Venoms Molecular Dynamics Simulation General Biochemistry Genetics and Molecular Biology Cone snail 03 medical and health sciences Antigens CD Biochemistry and Chemical Biology parasitic diseases medicine Animals Humans General Immunology and Microbiology Conus geographus Insulin Conus Snail Insulin Receptor Binding biology.organism_classification Hypoglycemia Receptor Insulin Insulin receptor Disease Models Animal 030104 developmental biology biology.protein sense organs Other 030217 neurology & neurosurgery |
| Zdroj: | eLife, Vol 8 (2019) eLife |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|