Fish-hunting cone snails add a unique form of insulin to the venom cocktail they use to disable their fish prey, according to a new study.

The Geography cone snail (Conus geographus) attempting to capture fish prey; as the snails approach potential prey, they release a specialized insulin into the water, along with neurotoxins that inhibit sensory circuits, resulting in hypoglycemic, sensory-deprived fish that are easier to engulf with their large, distensible false mouths; once engulfed, powerful paralytic toxins are injected by the snail into each fish. Image credit: Jason Biggs / Baldomero Olivera.
“It is very unlikely that it is serving a different purpose,” said Dr Helena Safavi-Hemami from the University of Utah, who is the first author of a paper published in the Proceedings of the National Academy of Sciences.
“This is a unique type of insulin. It is shorter than any insulin that has been described in any animal. We found it in the venom in large amounts,” added study senior author Prof Baldomero Olivera of the University of Utah.
Cone snails are a large genus of small to large predatory gastropod mollusks.
They are abundant in most tropical marine waters, especially around coral reefs. Each species makes a distinct repertoire of venom compounds, mixtures that have evolved to target particular prey.
The Geography cone snail (Conus geographus) – a species of cone snail that has killed dozens of people in accidental encounters – traps fish by releasing a blend of immobilizing venoms into the water, according to the prevailing hypothesis.
The species protrudes a stretchy mouth-like part and aims it like a gun barrel at fish, which become disoriented and stop moving even as the snail’s mouth part slowly advances and engulfs the fish.
Seeking to understand how the cone snail springs its slow-motion trap, Dr Safavi-Hemami, Prof Olivera and their colleagues searched the gene sequences of all of the proteins expressed in the venom gland of the Geography cone snail.
They found two sequences that looked surprisingly similar to that of the hormone insulin, used by humans and other vertebrate animals to regulate energy metabolism.
The insulin genes were more highly expressed in the venom gland than genes for some of the established venom toxins.
One sequence proved very similar to that of fish insulin. Chemical analysis of venom confirmed that it contained abundant amounts of this insulin.
The type of insulin found in venom glands (consists of 43 amino acid building blocks, fewer than any known insulin) seems to match the prey of a given cone snail. Fish insulin was present in the venoms of Conus geographus and Conus tulipa, which both practice the same fish-trapping method.
But the team found no evidence of fish insulin in the venom of five species of fish-eating cone snails that are ambush hunters that attack with a harpoon-like organ. Nor did they find fish insulin in the venom of cone snails that prey on mollusks or worms.
For more clear-cut evidence that snails use insulin as a weapon, the scientists came up with a fast way to synthesize enough of the insulin to directly test its effects on fish.
A synthetic form of the snail insulin, when injected into zebrafish, caused blood glucose levels to plummet. The insulin also disrupted swimming behavior in fish exposed through water contact, as measured by the percentage of time spent swimming and frequency of movements.
The team proposes that adding insulin to the mix of venom toxins enabled predatory cone snails to disable entire schools of swimming fish with hypoglycemic shock.
_____
Helena Safavi-Hemami et al. Specialized insulin is used for chemical warfare by fish-hunting cone snails. PNAS, published online January 20, 2015; doi: 10.1073/pnas.1423857112