A molecule other animals use to control insulin release has evolved a second role in platypus venom. In the process, it has been modified in a way that may make it suitable as a treatment for type 2 diabetes.
Like other mammals, birds, and reptiles, humans use the hormone glucagon-like peptide-1 (GLP-1) to stimulate the release of insulin, which in turn lowers blood sugar. GLP-1 is quickly degraded within the body, being destroyed by the DPP-4 enzyme, but it's much too quickly for people with type 2 diabetes. The search for a longer-lasting version of GLP-1 has already seen a similar molecule in the venom of the Gila monster become the leading diabetes drug Byetta.
A team led by the University of Adelaide's Professor Frank Grützner thought it would be interesting to study GLP-1 in monotremes (platypus and echidna), as these represent the closest surviving relatives of the first mammals. They noted previous research indicating the monotreme digestive system differs from other mammals.
What Grützner and his colleagues revealed in Scientific Reports is even more interesting than they expected. Both the platypus and the echidna have a version of GLP-1 that is used both for glucose regulation and venom. Stranger still, they use the same gene to produce this molecule, rather than duplicating the gene and eventually having the two versions evolve in different directions, as the Gila monster did.
Grützner explained to IFLScience that GLP-1 became incorporated into platypus venom. A swift spike with a platypus spur will cause a sharp drop in the blood sugar of the victim – usually a rival male rather than predators or prey, since the venom is only produced during mating season.
At some point, the platypus' GLP-1 changed to resist DPP-4, making it more effective as a venom. If GLP-1 was too long-lasting in the gut, however, it would keep sugar levels excessively low, so a new method of breaking it down, unique to monotremes, evolved. This replacement appears to operate more slowly than the conventional one that operates in other animals, but from a medical perspective that's not important. Since humans lack the enzymes that monotremes use to break down GLP-1, it would probably survive long enough in the human body to be an effective diabetes treatment.
Platypus venom is notoriously painful – it won't kill you, but you might wish it did. However, Grützner told IFLScience the pain comes from other molecules in a very “complex cocktail”. Monotreme GLP-1 will need much testing before it can be prescribed, but there is no obvious reason why it shouldn't be a safe and effective treatment for one of the most common diseases of our era.
Not bad for a species that zoologists once considered a hoax.
