Plain Language Summary: Insulin is a hormone critical for maintaining healthy 
blood sugar levels in humans. When the insulin system becomes faulty, blood 
sugar levels become too high, which can lead to diabetes. At the moment, the 
only effective treatment for one of the major types of diabetes are daily 
insulin injections. However, designing fast-acting insulin drugs has remained a 
challenge. Insulin molecules form clusters (so-called hexamers) that first have 
to dissolve in the body to activate the insulin receptor, which plays a key role 
in regulating the blood sugar levels throughout the body. This can take time and 
can therefore delay the blood-sugar control. In 2015, researchers discovered 
that the fish-hunting cone snail Conus geographus uses a specific type of 
insulin to capture its prey – fish. The cone snail releases insulin into the 
surrounding water and then engulfs its victim with its mouth. This induces 
dangerously low blood sugar levels in the fish and so makes them an easy target. 
Unlike the human version, the snail insulin does not cluster, and despite 
structural differences, can bind to the human insulin receptor. Now, 
Ahorukomeye, Disotuar et al. – including some of the authors involved in the 
previous study – wanted to find out whether other fish-hunting cone snails also 
make insulins and if they differed from the one previously discovered in C. 
geographus. The insulin molecules were extracted and analyzed, and the results 
showed that the three cone snail species had different versions of insulin – but 
none of them formed clusters. Ahorukomeye, Disotuar et al. further revealed that 
the snail insulins could bind to the human insulin receptors and could also 
reverse high blood sugar levels in fish and mouse models of the disease. This 
research may help guide future studies looking into developing fast-acting 
insulin drugs for diabetic patients. A next step will be to fully understand how 
snail insulins can be active at the human receptor without forming clusters. 
Cone snails solved this problem millions of years ago and by understanding how 
they have done this, researchers are hoping to redesign current diabetic 
therapeutics. Since the snail insulins do not form clusters and should act 
faster than currently available insulin drugs, they may lead to better or new 
diabetes treatments.