scholarly journals Decision letter: Fish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor

2018 ◽  
Keyword(s):  
Insulin Receptor ◽  
Rich Source ◽  
Cone Snail

scholarly journals Author response: Fish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor

2018 ◽  
Author(s):  
Peter Ahorukomeye ◽  
Maria M Disotuar ◽  
Joanna Gajewiak ◽  
Santhosh Karanth ◽  
Maren Watkins ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Rich Source ◽  
Author Response ◽  
Cone Snail

scholarly journals Fish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Peter Ahorukomeye ◽  
Maria M Disotuar ◽  
Joanna Gajewiak ◽  
Santhosh Karanth ◽  
Maren Watkins ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Rich Source ◽  
Cone Snail ◽  
Lower Blood Glucose ◽  
Human Insulin Receptor ◽  
Novel Drugs ◽  
Lower Blood ◽  
Treatment Of Diabetes ◽  
Cone Snails ◽  
Insight Into

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.

scholarly journals Visualization of Insulin Receptor Activation by a Novel Insulin Analog with Elongated A Chain and Truncated B Chain

2021 ◽  
Author(s):  
Xiaochun Xiong ◽  
Alan Blakely ◽  
Jin Hwan Kim ◽  
John Menting ◽  
Ingmar Schafer ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Receptor Activation ◽  
Structural Features ◽  
Biochemical Properties ◽  
Asymmetric Structure ◽  
Binding Modes ◽  
Cone Snail ◽  
Human Insulin Receptor ◽  
A Chain ◽  
Receptor Conformation

Abstract Cone snail venoms contain a wide variety of bioactive peptides, including insulin-like molecules with distinct structural features, binding modes, and biochemical properties. Here, we report a fully active humanized cone snail venom insulin with an elongated A chain and a truncated B chain, and use cryo-electron microscopy and protein engineering to elucidate its interactions with the human insulin receptor ectodomain. We reveal how an extended A chain can compensate for deletion of B-chain residues, which are essential for activity of native insulin but also compromise therapeutic utility by delaying the onset action, suggesting approaches to develop improved therapeutic insulins. Curiously, a receptor conformation present in low abundance adopts a highly asymmetric structure that displays novel coordination of a single humanized venom insulin using elements from both of the previously characterized site 1 and site 2 interactions.

Acquired hypermethylation of the hypothalamic insulin receptor promoter in neonatally overfed rats

2009 ◽  
Vol 213 (S 01) ◽  
Author(s):  
T Harder ◽  
K Roepke ◽  
T Ziska ◽  
A Harder ◽  
JW Dudenhausen ◽  
...  
Keyword(s):  
Insulin Receptor

Laricifomes officinalis – a rich source of pharmacologically active triterpenes

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381 ◽  
Author(s):  
S Sturm ◽  
K Gallmetzer ◽  
A Friedl ◽  
B Waltenberger ◽  
V Temml ◽  
...  
Keyword(s):  
Rich Source ◽  
Pharmacologically Active
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