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Monotreme Venom’s Potential as a Diabetes Drug

Remarkable evolutionary changes to insulin regulation in two of the nation’s most iconic native animal species – the platypus and the echidna – could pave the way for new treatments for type 2 diabetes in humans.

A study published in Scientific Reports has reported that the same hormone produced in the gut of the platypus to regulate blood glucose is also surprisingly produced in its venom.

The hormone, known as glucagon-like peptide-1 (GLP-1), is normally secreted in the gut of humans and other animals, stimulating the release of insulin to lower blood glucose. However, GLP-1 typically degrades within minutes.

In people with type 2 diabetes, the short stimulus triggered by GLP-1 isn’t sufficient to maintain a proper blood sugar balance. As a result, medication that includes a longer-lasting form of the hormone is needed to help provide an extended release of insulin.

“Our research team has discovered that monotremes – our iconic platypus and echidna – have evolved changes in the hormone GLP-1 that make it resistant to the rapid degradation normally seen in humans,” says co-lead author Prof Frank Grützner of The University of Adelaide. “We’ve found that GLP-1 is degraded in monotremes by a completely different mechanism.

“Further analysis of the genetics of monotremes reveals that there seems to be a kind of molecular warfare going on between the function of GLP-1, which is produced in the gut, but surprisingly also in their venom.”

The platypus produces a powerful venom during the breeding season, and this is used by males competing for females. “We’ve discovered conflicting functions of GLP-1 in the platypus: in the gut as a regulator of blood glucose, and in venom to fend off other platypus males during breeding season,” says co-lead author A/Prof Briony Forbes of Flinders University. “This tug-of-war between the different functions has resulted in dramatic changes in the GLP-1 system.

“The function in venom has most likely triggered the evolution of a stable form of GLP-1 in monotremes. Excitingly, stable GLP-1 molecules are highly desirable as potential type 2 diabetes treatments,” she says.

GLP-1 has also been discovered in the venom of echidnas. While the platypus has spurs on its hind limbs for delivering a large amount of venom to its opponent, there is no such spur on echidnas. “The lack of a spur on echidnas remains an evolutionary mystery, but the fact that both platypus and echidnas have evolved the same long-lasting form of the hormone GLP-1 is in itself a very exciting finding,” Grützner says.