An at times urgent need for insulin has given rise to quick-fire solutions that can take effect in as few as 15 minutes, but in a scenario where every second can make a difference there is always room for improvement. This has led scientists to look for an even faster-acting insulin from a notoriously slow-moving source, finding the insulin in a certain type of snail venom can begin working in a third of the time of the fastest insulins currently on the market.
The cone snail is quite the cunning ocean predator. You certainly won't catch it chasing down its prey, but these sea-dwelling mollusks have a pretty neat trick up their shells in the form of venomous cocktails that can be released into the water to paralyze fish.
Some snails use venom to overload the fish's nervous system, but others, like the cone snail, secrete insulin as part of this mix. This drives down the blood-sugar levels in nearby fish and induces a state of hypoglycemic sedation, leaving them stunned and the snails with an easy dinner. This fast-acting insulin was of particular interest to biologist Helena Safavi, who studies venom cocktails at the University of Utah with a view to discovering new kinds of drugs.
"You look at what venoms animals make to affect the physiology of their prey, and you use that as a starting point," she says. "You can get new ideas from venoms. To have something that has already been evolved — that's a huge advantage."
Synthetic insulins mimic the effects of natural insulins in the pancreas by boosting the body's uptake of glucose. But it's a little more complicated than that. An insulin molecule in the pancreas is split into an A and a B region, and part of the B region causes individual molecules to clump together. When it comes to injected insulin, these molecules must break apart before the drug can perform its role, which is why even the fastest acting versions take some time to set in.
Studying the insulin produced by the cone snail, the researchers found the creatures have evolved insulin molecules that actually lack part of the B region that makes them stick together, allowing them to act faster in helping trap their prey.
Comparison of the structures of insulin in the cone snail (red/white) and in humans (blue/white and green). The green B-chain terminal segment is absent in the cone snail
Putting the insulin to the test in the lab, the researchers found that while it was not as effective as human insulin, it was perfectly able to latch onto human receptors. They point out that fish are effected almost instantly because the insulin passes over their gills, and while the injecting it into humans is expected to take longer, they expect that could work in as little as five minutes.
The scientists will now continue studying the structure of the cone snail's insulin as a way of modifying and improving the insulin currently used in humans.
"The next step in our research, which is already underway, is to apply these findings to the design of new and better treatments for diabetes, giving patients access to faster-acting insulins," says Safavi.
The team's research was published in the journal Nature Structural and Molecular Biology.