Platypus venom may contain a better version of GLP-1 receptor agonist

The GLP-1 analogue exenatide (Byetta) was developed from the venom of a Mexican lizard and Australian scientists are now aiming to go one better and source a superior incretin mimetic from the duck billed platypus.

Adelaide researchers have already characterised a unique form of glucagon-like peptide-1 from the monotreme and are now investigating whether the Australian version may be more potent and more resistant to metabolic breakdown than current GLP-1 receptor agonists used to treat diabetes.

The discovery of a unique form of the GLP-1 receptor agonist came from the sequencing of the platypus genome in 2008 led by biologist Professor Frank Grutzner, Head of the University of Adelaide’s Mammalian Reproduction Group.

Now Professor Grutzner is working in collaboration with Flinders University, Monash University, the South Australian Health and Medical Research Institute and the Royal Adelaide Hospital to conduct a study into whether the platypus hormone could be more effective and sustained in action than current medication.

The GLP-1 receptor agonist exenatide currently used in diabetes is a synthetic form of the hormone exendin-4 that occurs naturally in the saliva of the Gila monster, a large venomous lizard native to the southwestern United States and northwestern Mexico.

The development of the drug led scientists to look for different forms of GLP in other animals – including monotremes.

“Male platypuses produce venom during the breeding season, and can deliver the venom from their hind spurs. We were surprised to see GLP-1 present in venom and think that this may have led to a more effective hormone,”says Professor Grutzner.

“One of the most amazing discoveries of the platypus genome project was the massive loss of genes important for digestion and metabolic control – these animals basically lack a functional stomach,” he adds.

“More recently we discovered that monotreme GLP-1 has changed radically in these animals, due to its dual function in both the gut and venom.”

The Adelaide researchers found unique changes in GLP-1 of monotreme mammals that result in resistance to DPP-4 cleavage. They also discovered that monotremes evolved an alternative mechanism to degrade GLP-1.

“We already know that their GLP-1 works differently, and is more resistant to the rapid degradation normally seen in humans. Maybe this iconic Australian animal holds the answer to a more effective and safer management option for metabolic diseases including diabetes.”

The effects of platypus-derived GLP-1 are now being explored in detail thanks to a $200,000 grant from Medvet Science, the medical research support and commercialisation arm of the Central Adelaide Local Health Network.

“This discovery has the potential to produce significant benefits for human health by bringing industry, leading academic researchers and clinical expertise together,” said Medvet Science’s Managing Director and CEO, Mr Greg Johansen.

“This is the first step towards testing the clinical relevance of platypus GLP-1. We believe it’s a project with great commercial potential and an example of the world-class research being conducted right here in South Australia,” Mr Johansen said.

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