What do diabetics and cone snails have in common? The need for insulin

 

Paper: Safavi-Hemami, H., Gajewiak, J., Karanth, S., Robinson, S. D., Ueberheide, B., Douglass, A. D., … Olivera, B. M. (2015). Specialized insulin is used for chemical warfare by fish-hunting cone snails. Proceedings of the National Academy of Sciences of the United States of America, 1–6. doi:10.1073/pnas.1423857112

Background

Venom is a common strategy for both hunting and defense in the animal kingdom – you’re probably familiar with rattlesnake venom, or the deadliest venom of all, that from the box jelly. Those venoms shut down prey by releasing neurotoxins, special chemicals designed to derail the normal functions of the brain. Neurotoxins render the prey unconscious, paralyzed, or worse – dead. A team of researchers centered in Utah found that cone snails, another animal that uses venom, doesn’t use the neurotoxin approach – instead, they found that cone snails inject the water with insulin to catch their prey.

Vertebrate insulin is very different from invertebrate insulin: a human’s insulin, then, is very different from insulin in an invertebrate like the cone snail. Both hormones perform the same basic function of regulating metabolism and energy, but the size and structure of the hormone are different for each group. Vertebrate insulin is only used in metabolism, whereas invertebrate insulin is used for all kinds of things – brain signaling, memory, reproduction, and growth. Invertebrate insulin, perhaps because it has more variable functions, is a larger molecule than vertebrate insulin, so it’s easy to tell the two apart with molecular techniques.

That matters because the researchers, while they were looking into the toxin released by the cone snail, realized that the insulin the cone snail was releasing was very similar in structure to vertebrate insulin. The finding was surprising – the researchers expected the hormone to have an invertebrate structure because the cone snail is an invertebrate. They soon found the reason: the insulin wasn’t for the cone snail, it was for the cone snail’s vertebrate prey.

 

 

 

 

 

 

 

 

The researchers sequenced the insulin hormone, which breaks the molecule down to its sequence of individual amino acids, much like the sequencing of DNA. Once they did that, they found that the sequence they observed was most similar to fish insulin. That led them to hypothesis that the insulin released by the cone snail was intended to have an effect on the fish that the cone snails eat.

Methods and Results

To test that hypothesis, researchers sequenced the amino acids of several different types of cone snails that had different food preferences: one group of snails that ate fish, another that ate other molluscs, and a third that ate worms. They found that only the fish hunting snails had the insulin that closely mimicked the structure of the vertebrate insulin, suggesting that the insulin was used for feeding. The snails that hunted other molluscs or worms only had invertebrate insulin.

To further test this hypothesis, the researchers synthesized the insulin from a cone snail and put it in the same environment as a model prey species, a zebrafish. First, they artificially increased the blood sugar of the zebrafish by injecting them with a mild poison called steptozotocin. Once the fish all had high blood glucose, the researchers injected the fish with the insulin from the cone snail. They observed a significant decrease in blood sugar, suggesting that the cone snail’s insulin venom lowered the blood sugar of the fish.

 

 

 

 

 

 

 

 

 

 

Why would the cone snails want to lower the blood sugar of the fish? To answer that question, the researchers injected the hormone into the water to see what behavior the fish would exhibit. They found that the fish are less energetic once they have lower blood sugar: they swam for a shorter amount of time and less frequently than fish with normal blood sugar. Slowing the fish down like that would allow the cone snail (who, after all, is still a snail!) to catch the quicker-moving fish.

 

 

 

 

 

 

 

 

 

Discussion and Significance

This study allowed researchers to figure out one aspect of how the cone snail’s venom helps it hunt effectively. These cone snails stalk schools of small fish that hide in reef crevices at night, and by releasing a type of insulin similar to what the fish already has, the snail succeeds at slowing the fish down so that the snail can catch them. When they have low blood sugar, the fish become weak and sluggish, making them an easy target for the snail.

This study is especially interesting because insulin has never been reported in any other venom. A similar hormone, isolated from the gila monster’s saliva, has been also been shown to lower the blood sugar of prey. As a result, the hormone (exendin) was developed into a commercial drug that helps treat diabetes. Seeing the same mechanism in cone snails might lead to a similar pharmaceutical application.