Marine snail inspires fast-acting injectable insulin for better diabetes control

For millions of people with diabetes, it's important that they have a good supply ofinsulin. For some ocean-dwelling predator, it's a weapon. A fish-hunting cone snail can drop its prey's blood sugar so quickly that it becomes paralyzed and defenseless. Scientists at the University of Utah Health, the University of Utah, and the University of Copenhagen have been inspired by that phenomenon.

A new type ofinsulin is based on venom from a marine snail, according to a report in the journal Nature Chemical Biology. By introducing biochemical features that enable the snail's insulin to start working quickly, they have created a modified form of human insulin that they hope could give patients with diabetes better, more immediate control over their blood sugar.

There was an idea that if one could design a very rapidly acting insulin analog, one could get better control of blood sugar levels in people with diabetes. She is a co-corresponding author on the study with two other people.

The molecule is a promising candidate. It has shown an unexpected strategy for converting humaninsulin into a fast-acting compound.

Snails have quick and easy-to-manufacture blood thinners.

Normally, humaninsulin is produced and stored in the pancreas until it is needed to manage blood sugar and energy levels. Individual molecule ofinsulin come together, linking up first into pairs and then into groups of six. For people who rely on injections, the molecule's tendency to pair up is an impediment. The injection site can't be used to move the drug to the bloodstream. This creates a delay that can make it difficult for people with diabetes to keep their blood sugar within the optimal range, increasing the risk of complications.

The research team was interested in the cone snails because they don't form. It wants to have something that paralyzes fish very quickly. It is a single drug that acts in the fish.

Since that work began, patients have been able to get some of the less denseinsulins that form fewer clusters. The therapeuticinsulins do form pairs, but they separate more readily than humans.

Fishing for answers.

In 2020, a team led by Chou, a professor at U of U Health, achieved that same shift to the monomeric form. Conusgeographus is the only cone snail that makesinsulin.

Each species of cone snails has a different cocktail of toxins that it uses to subdue its prey. Several of the cone snail venoms found at the U of U contained a type of molecule that was related to the human body. Even though it was fast-acting and cluster-free, one of those venomousinsulins was structured differently than the one made by Conusgeographus.

The team was able to recognize Conus kinoshitai's unique biochemical tactics, which led to the development of a new hybridinsulin. The new molecule does not form clusters like the original one, but it does have the ability to bind to the humaninsulinreceptor. The venom from one of the two cone snail species can be used to create two hybrid insulin molecules, which hold the same promise as potential therapies.

It took a graduate student in Hill's lab to reveal how the new hybridinsulin works. The structure of the newinsulin and how it interacts with itsreceptor were visualized using cryo-electromagnetic microscopy.

To create the snail-human insulin hybrid, the segment that links the molecule to one another has been removed. The Hill lab has a structural analysis that explains how the newinsulin works.

Understanding how the two molecule interact will help guide further development of potential fast-acting insulins.

The way in which this study spans a wide range of science, starting with the study of a fascinating question in animal behavior, is beautiful.

He says that the research has opened an exciting avenue for developing better therapies for people with diabetes.

More information: Xiaochun Xiong et al, Symmetric and asymmetric receptor conformation continuum induced by a new insulin, Nature Chemical Biology (2022). DOI: 10.1038/s41589-022-00981-0 Journal information: Nature Chemical Biology Citation: Marine snail inspires fast-acting injectable insulin for better diabetes control (2022, March 15) retrieved 17 March 2022 from https://phys.org/news/2022-03-marine-snail-fast-acting-insulin-diabetes.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.