PUBLICATION
Fish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor
- Authors
- Ahorukomeye, P., Disotuar, M.M., Gajewiak, J., Karanth, S., Watkins, M., Robinson, S.D., Flórez Salcedo, P., Smith, N.A., Smith, B.J., Schlegel, A., Forbes, B.E., Olivera, B., Hung-Chieh Chou, D., Safavi-Hemami, H.
- ID
- ZDB-PUB-190213-6
- Date
- 2019
- Source
- eLIFE 8: (Journal)
- Registered Authors
- Karanth, Santhosh, Schlegel, Amnon
- Keywords
- biochemistry, chemical biology, cone snail, diabetes, hypoglycemic shock, insulin, prey capture, venom
- MeSH Terms
-
- Animals
- Antigens, CD/chemistry
- Conus Snail/chemistry*
- Disease Models, Animal
- Humans
- Hypoglycemia/pathology
- Insulin/chemistry
- Insulin/genetics
- Insulin/metabolism*
- Mice
- Molecular Dynamics Simulation
- Mollusk Venoms/metabolism*
- Poisoning/pathology
- Poisons/metabolism*
- Receptor, Insulin/agonists*
- Receptor, Insulin/chemistry
- Zebrafish
- PubMed
- 30747102 Full text @ Elife
Citation
Ahorukomeye, P., Disotuar, M.M., Gajewiak, J., Karanth, S., Watkins, M., Robinson, S.D., Flórez Salcedo, P., Smith, N.A., Smith, B.J., Schlegel, A., Forbes, B.E., Olivera, B., Hung-Chieh Chou, D., Safavi-Hemami, H. (2019) Fish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor. eLIFE. 8.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping