Nav: Home

Snails' speedy insulin

September 12, 2016

University of Utah researchers have found that the structure of an insulin molecule produced by predatory cone snails may be an improvement over current fast-acting therapeutic insulin. The finding suggests that the cone snail insulin, produced by the snails to stun their prey, could begin working in as few as five minutes, compared with 15 minutes for the fastest-acting insulin currently available. Biologist Helena Safavi, co-author on a paper describing the cone snail insulin published September 12 in Nature Structural & Molecular Biology, says that studying complex venom cocktails can open doors to new drug discoveries.

"You look at what venoms animals make to affect the physiology of their prey, and you use that as a starting point," she says. "You can get new ideas from venoms. To have something that has already been evolved -- that's a huge advantage."

Along with colleagues from Australia, U biochemists Danny Chou and Maria Disotuar, and biologists Joanna Gajewiak and Baldomero Olivera contributed to the study.

Small and speedy

Human insulin is a hormone that is produced in the pancreas and secreted to aid in the body's uptake of glucose. The insulin molecule consists of an "A" region and a "B" region. Diabetes mellitus disorders arise from impairment of the body's normal production of insulin. The most effective treatment for diabetes is injection of synthetic insulin.

But a part of the B region causes insulin molecules to stick together and form aggregations of six insulin molecules. It's how insulin is stored in the pancreas. But injected insulin must de-aggregate into individual molecules before doing a person any good - and that process can take up to an hour. The fastest-acting insulin on the market, Humalog, still takes 15-30 minutes to become active. "The ideal scenario would be to take the region off of the B chain" Safavi says. "But then you completely abolish insulin activity."

Chou, Safavi, and colleagues found that insulin produced by the cone snail Conus geographus lacked the segment of the B region that causes aggregation. Tests on insulin receptors in the lab showed that although the snail insulin was less effective than human insulin, it was still effective, and could possibly start acting in five minutes.

Insulin as a weapon

The Conus geographus snail is a predatory cone snail, eating fish. C. geographus and its relatives have developed complex brews of venoms to rapidly paralyze prey fish. Some snails use venom to overload the fish's nervous system, sending it into "excitotoxic shock." Others, including C. geographus, secrete insulin, alongside other compounds, into the water, causing the blood sugar in nearby fish to plummet and sending the fish into hypoglycemic sedation. Once the fish is stunned, the snail engulfs and consumes it.

In 2015, Safavi and U biology professor Baldomero Olivera describedC. geographus' so-called "weaponized insulin," suited for quick action. In a related paper published Aug. 16 in Molecular Biology and Evolution, Safavi and colleagues describe how weaponized insulins evolved rapidly to more effectively target prey.

"It makes sense because the snail has to very rapidly induce insulin shock in its fish prey, so it has evolved something very fast acting," Safavi says.

Putting snail insulin to work

Studying the structure of the cone snail insulin could help researchers modify human insulin to lose its self-aggregation but retain its potency, Safavi says. "Now we can look at the human insulin and see if we can make it more snail-like."

The team still needs to conduct more experiments to measure how quickly snail insulin, or a modified human insulin, would work when injected into an organism. Fish are affected almost instantly because the insulin passes over the gills. In humans, the process may take a few minutes longer.

Chou studies human insulin for use in an artificial pancreas device that could automatically deliver insulin in response to changing blood sugar levels, much as the natural organ does. The first generation of such a device may be available as soon as next year. Cone snail-inspired insulin, although "still not as good as we want for human use," Chou says, could replace the current fast-acting insulin used in artificial pancreas development.

Bio-inspiration

"It's really about learning from nature," Chou says. Safavi agrees. "People think it's easy to make drugs," she says. "But where do you start? You have to have some kind of idea of what a drug should look like, what kind of properties the drug should have, so it's very difficult to design novel drugs. That's why we use the snail venom system."
-end-
This press release and images can be found here.

After the embargo lifts, the full paper can be found here.

Funding for the study was provided by the National Health and Medical Research Council of Australia, the National Institutes of Health, USTAR and the European Commission.

University of Utah

Related Insulin Articles:

Diabetes patients still produce insulin
Some insulin is still produced in almost half of the patients that have had type 1 diabetes for more than ten years.
New type of insulin-producing cell discovered
In people with type I diabetes, insulin-producing beta cells in the pancreas die and are not replaced.
A sustained and controllable insulin release system
Researchers from Kumamoto University, Japan have developed an insulin release system with sustained and controllable delivery.
Chemically modified insulin is available more quickly
Replacing a hydrogen atom by an iodine atom in insulin, the hormone retains its efficacy but is available more rapidly to the organism.
Insulin resistance and polycystic ovary syndrome
Insulin resistance represents a major issue for people with polycystic ovary syndrome (PCOS), an endocrine disorder which is very common in young women, according to a new analysis of available data carried out by Dr.
Insulin resistance reversed by removal of protein
By removing the protein galectin-3 (Gal3), a team of investigators led by University of California School of Medicine researchers were able to reverse diabetic insulin resistance and glucose intolerance in mouse models of obesity and diabetes.
Snails' speedy insulin
University of Utah researchers have found that the structure of an insulin molecule produced by predatory cone snails may be an improvement over current fast-acting therapeutic insulin.
Discovery could lead to treatment to better regulate insulin
A recent discovery made by an Iowa State University professor and a team of researchers holds promise for those who are obese or diabetic and do not benefit from medications to regulate their glucose and insulin levels.
Insulin-sensitive fat leads to obesity
SORLA is a protein that influences the balance of metabolic processes in adipose tissue, a particular form of fat.
Is an insulin pump the best therapy for everyone with type 1 diabetes?
Insulin pump therapy contributes to better blood glucose control in type 1 diabetes and, as pump technology continues to improve and become part of sensor-controlled feedback and artificial pancreas systems, essentially all patients would benefit from their capabilities according to a Commentary published in Diabetes Technology & Therapeutics.

Related Insulin Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Changing The World
What does it take to change the world for the better? This hour, TED speakers explore ideas on activism—what motivates it, why it matters, and how each of us can make a difference. Guests include civil rights activist Ruby Sales, labor leader and civil rights activist Dolores Huerta, author Jeremy Heimans, "craftivist" Sarah Corbett, and designer and futurist Angela Oguntala.
Now Playing: Science for the People

#521 The Curious Life of Krill
Krill may be one of the most abundant forms of life on our planet... but it turns out we don't know that much about them. For a create that underpins a massive ocean ecosystem and lives in our oceans in massive numbers, they're surprisingly difficult to study. We sit down and shine some light on these underappreciated crustaceans with Stephen Nicol, Adjunct Professor at the University of Tasmania, Scientific Advisor to the Association of Responsible Krill Harvesting Companies, and author of the book "The Curious Life of Krill: A Conservation Story from the Bottom of the World".