Cone snail venom is deadly, but could now lead to better diabetes medication

The deadly venom of cone snails could be a key to developing better drugs to treat diabetes, according to a new study.

The toxin, which comes from one of the most poisonous creatures on Earth, could also lead to the development of new drugs for other diseases caused by hormonal disorders, according to the researchers.

They identified a component in the venom of Conus geographus that mimics a human hormone called somatostatin, which regulates blood sugar levels and several other hormones in the human body.

The team, led by scientists at the University of Utah in the US, said the somatostatin-like toxin helps the snail hunt down its prey. In humans, somatostatin acts like a brake pedal for many processes in the body, preventing blood sugar levels, the levels of several hormones and many other important molecules from rising to dangerous levels.

The cone snail venom consomatin has a similar effect – but consomatin is more stable and specific than the human hormone, making it a “promising” blueprint for drug development, according to the results published in the journal Nature Communications.

By measuring the interaction of consomatin with the targets of somatostatin in human cells in a Petri dish, the researchers discovered that consomatin interacts with one of the same proteins as somatostatin.

Importantly, however, somatostatin interacts directly with several proteins, while consomatin interacts with only one. Such finely tuned targeting means that the cone snail venom affects hormonally-mediated blood sugar levels, but not the levels of several other molecules.

They concluded that the cone snail venom was more targeted than most specific synthetic drugs used to regulate hormone levels, such as drugs used to regulate growth hormone.

Although the use of snail venom as a therapeutic agent can be dangerous, studying its structure could lead to the development of safe drugs against endocrine disorders.

Consomatin lasts much longer in the body than the human hormone because it contains an unusual amino acid that makes it difficult to break down. Studying this property would be useful for pharmaceutical researchers who want to develop drugs with long-lasting effects.

Lead author Professor Helena Safavi of the University of Utah says the precision of the toxin could be “extraordinarily useful” in treating disease.

“Venomous animals have fine-tuned venom components over the course of evolution to hit and disrupt a specific target in the prey. If you take a single component out of the venom mix and look at how it disrupts normal physiology, that pathway is often really relevant in disease.”

She described it as “a kind of shortcut” for medicinal chemists, since consomatin shares an evolutionary lineage with somatostatin, but the cone snail weaponized its own hormone over millions of years of evolution.

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Consomatine's lethal effect is due to its ability to prevent blood sugar levels from rising. It lowers blood sugar levels so quickly that the cone snail's prey becomes unresponsive. Then its second component prevents blood sugar levels from recovering.

“We believe that the cone snail evolved this highly selective toxin to work together with the insulin-like toxin to lower blood sugar to very low levels,” said Dr. Ho Yan Yeung of the University of Utah, the study's lead author.

She explained that the fact that several components of the cone snail's venom target blood sugar levels suggests that it may contain many other molecules that have a similar function.

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“This means that the venom may not only contain insulin and somatostatin-like toxins,” said Dr. Yeung. “It may also contain other toxins that regulate blood sugar levels.”

It may seem surprising that a snail is able to outperform the best human chemists in developing drugs, but Prof. Safavi says that in evolution, cone snails have time on their side.

“We have been trying to do medicinal chemistry and drug development for several hundred years, sometimes with poor results.”

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“Cone snails have had a lot of time to do this really well – and they’re just really good chemists.”

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