Please ensure Javascript is enabled for purposes ofwebsite accessibility

Cone snail, human insulin hybrid could lead to better diabetes treatments


A scuba diver holds a live specimen of Conus geographus collected during a night dive. Scientists used insulin extracted from this snail's venom to produce a hybrid form of fast-acting insulin that could work in humans. (Photo credit: Adam Blundell)
A scuba diver holds a live specimen of Conus geographus collected during a night dive. Scientists used insulin extracted from this snail's venom to produce a hybrid form of fast-acting insulin that could work in humans. (Photo credit: Adam Blundell)
Facebook Share IconTwitter Share IconEmail Share Icon

An international team of researchers, including University of Utah Health scientists, report they have developed the world’s smallest, fully functional version of insulin.

The human hybrid insulin combines the potency of human insulin with the fast-acting potential of venom insulin produced by predatory cone snails. The finding, based on animal studies, could jumpstart the development of insulin treatments capable of improving the lives of those with diabetes, a press release stated.

Danny Hung-Chieh Chou, Ph.D., a U of U Health assistant professor of biochemistry and one of the study’s corresponding authors, said in a prepared statement:

We now have the capability to create a hybrid version of insulin that works in humans and that also appears to have many of the positive attributes of cone snail insulin. That’s an important step forward in our quest to make diabetes treatment safer and more effective.

The study appears in Nature Structural and Molecular Biology. It states that as cone snails slither across coral reefs, they look for prey and some of them release plumes of toxic venom that contain a unique form of insulin into the surrounding water. The insulin causes fish blood glucose levels to plummet, temporarily paralyzing their prey. As the fish flounders, the snail emerges from its shell to swallow the subdued victim whole, the report states.

According to a news release, researchers found that insulin derived from cone snail venom lacks a “hinge” component that causes human insulin to aggregate or clump together so it can be stored in the pancreas. These aggregates must break up into individual molecules before they can begin to work on blood sugar, a process that can take up to an hour. Since cone snail insulin doesn’t aggregate, it is in essence primed and ready to work on the body’s biochemical machinery almost immediately, the news release stated.

The researchers investigated ways to transform the insulin that cone snails use into a different form: one that people who have Type-1 diabetes could use to rapidly restore equilibrium in their bodies. The researchers thought this was possible because cone snail insulin essentially has the same basic structure or “backbone” as human insulin. However, they faced a dilemma: the snail’s insulin is far less potent than human insulin. In fact, the researchers suspect that humans would require 20 to 30 times more of the cone snail insulin to lower their blood sugar levels.

In the new study, Chou and colleagues sought to overcome these problems. They used structural biology and medicinal chemistry techniques to isolate four amino acids that help the snail insulin bind to the insulin receptor. Then, they created a truncated version of a human insulin molecule without the region responsible for clumping. The team integrated modified versions of these amino acids into the human molecule in hopes of creating a hybrid that does not clump and binds the human insulin receptor with high potency, the news release stated.

In tests with laboratory rats, this hybrid insulin molecule, which the scientists call “mini-insulin,” interacted with insulin receptors in ways that cone snail insulin doesn’t. These new interactions bound mini-insulin to insulin receptors in the rat’s body just as strongly as normal human insulin would. As a result, mini-insulin had the same potency as human insulin but acted faster.

“Mini-insulin has tremendous potential,” Chou was quoted as saying in the news release. “With just a few strategic substitutions, we have generated a potent, fast-acting molecular structure that is the smallest, fully active insulin to date. Because it is so small, it should be easy to synthesize, making it a prime candidate for the development of a new generation of insulin therapeutics.”

Loading ...