Snail venom hope for diabetics

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Associate Professor Briony Forbes at her laboratory at Flinders Medical Centre.

New research has found that venom extracted from a species of marine cone snail could hold the key to developing “ultra-fast-acting” insulins, leading to more efficient therapies for diabetes management.

Researchers from Australia and the US have successfully determined the three dimensional structure of a cone snail venom insulin, revealing how this highly efficient natural protein called Con-Ins G1 can operate more rapidly than human insulin.

The team was a collaborative study between Flinders University, the Walter and Eliza Hall Institute (WEHI), University of Utah, the Monash Institute of Pharmaceutical Sciences and La Trobe University, .

Flinders University’s School of Medicine medical biochemistry researcher Associate Professor Briony Forbes helped to analyse the characteristics of the insulin-like peptide molecules from the venom of marine cone snails common to northern Australia. Her research demonstrated that Con-Ins G1 is able to bind to human insulin receptors, signifying the potential for its translation into a human therapeutic.

Published today in Nature Structural and Molecular Biology, the team’s findings build on earlier studies which reported that the marine cone snail Conus geographus used an insulin-based venom to trap its prey.

Unsuspecting fish prey would swim into the invisible trap and immediately become immobilised in a state of hypoglycemic shock induced by the venom.

The World Health Organization forecasts the number of people worldwide with diabetes has gone up from 108 million in 1980 to 422 million in 2014 with the rates of diabetes rising faster in middle- and low-income countries. The WHO estimate that by 2030, diabetes will be the seventh leading cause of death worldwide.

Dr Helena Safavi-Hemami, from the University of Utah, said the Flinders researchers showed that the cone snail insulin can ‘switch on’ human insulin cell signalling pathways following the successful binding to human receptors.

“We were thrilled to find that the principles of cone snail venom insulins could be applied to a human setting,” Dr Safavi-Hemami said.

“The next step in our research, which is already underway, is to apply these findings to the design of new and better treatments for diabetes, giving patients access to faster-acting insulins.”

Associate Professor Lawrence, from the WEHI who co-led the study, is a specialist in the structure of insulins and their receptors. He said the research teams utilised the Australian Synchrotron to create and analyse the three-dimensional structure of this cone snail venom insulin protein with exciting results.

“We found that cone snail venom insulins avoid the structural changes that human insulins undergo in order to function – they are essentially primed and ready to bind to their receptors,” Associate Professor Lawrence said, adding human insulins could be considered “awkward” by comparison.

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The venomous marine cone snail under water. Photo courtesy of Professor B. Olivera, University of Utah.

Associate Professor Forbes said the discoveries mean that a new kind of rapid-acting insulin could be made to better manage blood-sugar levels in diabetic individuals.

“It’s a pretty unique approach as no one has used the cone snail insulin before,” she says.

“Better insulin has to come from understanding how it works through its receptor and this research gives us new insights into how these proteins act.”

The research is supported by the National Health and Medical Research Council.

In Australia about 1.7 million people have diabetes, with the annual cost impact of diabetes estimated at $14.6 billion with an additional 280 Australian developing diabetes every day.

About half of all people with diabetes will be treated with insulin at some stage of their disease, including about 15% of all cases – people with type 1 diabetes – totally dependent on insulin therapy. Insulin is currently manufactured in yeast or bacteria and is effective but could be improved.

It is estimated that by 2035, global demand for insulin will be 16,000 tonnes. Insulin with more rapid action is required to provide better blood glucose control.

 

 

 

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