Lizard Saliva Reduces Sugar Overload

the black and tan bumpy head of a gila monster

Biological Strategy

Gila monster

Sam Stier

Image: Andrew DuBois / Flickr / CC BY NC - Creative Commons Attribution + Noncommercial

Regulate Cellular Processes

Cells are the basic building blocks of all living systems, so cellular processes dictate how physiological processes occur within those systems. Cells (whether entire unicellular organisms or parts of multicellular living systems) grow, metabolize nutrients (that is, chemically transform them), produce proteins and enzymes, replicate, and move. Cells as part of multicellular systems rarely act alone, instead having ways to signal to start and complete simple to quite complex interactions. How skin heals is a good example of the role of cellular processes. Blood cells called platelets release clotting factors to stop the bleeding; white blood cells rid the area of foreign materials and release molecules to coordinate healing; cells called fibroblasts start rebuilding using proteins called collagen; new blood vessels form; and skin cells called keratinocytes create the new surface.

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Maintain Homeostasis

When a living system is in homeostasis, it means that internal conditions are stable and relatively constant. For example, a human’s internal temperature is approximately 37 degrees Celsius (98.6 degrees Fahrenheit) unless there’s an illness. The human body maintains this temperature despite external ambient temperature. However, as with all physiological processes, maintaining homeostasis requires communication and coordination. So living systems have ways to detect changes from the norm, mechanisms to cause an adjustment, and negative feedback connections between the two. A desert lizard called the Gila monster offers a good example of maintaining homeostasis. The lizard goes from eating large meals to fasting for extended time periods. To maintain its blood sugar levels at a steady level, when food is scarce, its endocrine system releases a hormone that raises its blood sugar levels.

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Reptiles

Class Reptilia (“creeping”): Lizards, crocodiles, turtles, snakes

Reptiles retain some of the key characteristics that first enabled vertebrates to live permanently on land. They have dry skin covered in scales made of keratin that help prevent water loss. (Amphibians still need to stick close to water to keep their skin moist.) Many reptiles reproduce by laying eggs that are watertight and have a yolk, so eggs can develop on land while staying moist and nourished. Reptiles are also ectotherms, meaning they don’t produce their own body heat. This means they burn through energy much more slowly than “warm blooded” creatures of the same size. It also means that they need to keep warm to keep active, which is why you might see them spending a seemingly inordinate amount of time simply basking in the sun.

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A long-lasting molecule in the venomous saliva of gila monsters enables prolonged insulin production.

Introduction

With good meals few and far between in the scorching deserts striding the U.S.-Mexico border, gila monsters (Heloderma suspectum) need to be able to get as much out of each successful hunt as they can. Gorging themselves, young gilas can consume half their body weight in a single sitting. In order to extract maximum energy from the such meals can yield, the hardy reptiles need to keep their pancreases producing over extended periods of time. Such an ability could be a great help for diabetics.

Gilas might be best known for having a potentially deadly venomous bite, but their legacy may actually be for saving human lives, not endangering them.

The Strategy

When you ingest carbohydrates from things like bread, fruits, vegetables, and dairy, your blood sugar (glucose) rises. In order for your body to turn it into energy, this sugar has to enter your cells from your blood stream. Insulin, a produced by the , increases in your blood stream as soon as glucose appears. In type-I diabetics, the body prevents itself from producing enough insulin to do its job.

Insulin tells your cells to open up and accept the glucose inside. Once in your cells, glucose can be converted into energy for immediate use or stored for use later. You’re using glucose right now, just to have the energy to read these words.

Within minutes of eating, your body produces another molecule, glucagon-like 1 (GLP1), which signals your pancreas to start producing insulin. Supplemental GLP1 would therefore be a good candidate for treating diabetes, except for the fact that it lasts only minutes before enzymes in our bodies break it back down. Ideally, a GLP1-like substance might be discovered which our enzymes didn’t break down so quickly, so that it could boost insulin production more effectively in diabetics.

"[E]xendin-4 was discovered in 1992 in the gila monster, after a researcher noticed the gila’s venom caused the pancreas of bitten victims to swell."

The Potential

Such a substance, exendin-4, was discovered in 1992 in the gila monster, after a researcher noticed the gila’s venom caused the pancreas of bitten victims to swell. In the human body, exendin-4 mimics the insulin-promoting action of GLP1, but it isn’t susceptible to our bodies’ GLP1-destroying enzymes. Synthetic peptides identical to exendin-4 are now used by diabetics around the world, helping them produce adequate levels of insulin and enjoy normal, healthy lives.

Related Innovation

Innovation: Industry

Injectable Medication for Diabetics Inspired by the Gila Monster

AstraZeneca

Byetta from AstraZeneca is an insulin sensitizer that mimics proteins from Gila monster saliva to help Type 2 diabetics maintain glucose levels.

Last Updated May 17, 2018

References

Journal article

Isolation and characterization of exendin-4, and exendin-3 analogue, from Heloderma suspectum venom: further evidence for an exendin receptor on dispersed acini from guinea pig pancreas.

J Biol Chem. 1992 Apr 15;267(11):7402-5. | J Eng, W A Kleinman, L Singh, G Singh and J P Raufman

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