Solution to Faster Acting Insulin Identified in Snail Venom

A research of the crystalline 3-D structure of insulin produced from the venom of a marine snail shows a possible way to make insulin for the therapy of diabetes act more quickly.

Investigators from Australia and the United States have identified that the venom of Conus geographus consists of a highly effective natural protein – known as Con-Ins G1 – that operates quicker than human insulin.

They also identified that the protein is capable of attaching to human insulin receptors, indicating it could work as a therapy for diabetes.

The study team presents the results in the journal Nature Structural & Molecular Biology.

Diabetes is where the body either does not make sufficient insulin (type 1 diabetes) or cannot use it effectively (type 2 diabetes).

The human body requires insulin to enable glucose to enter cells for use as energy. If the body has inadequate insulin, or loses the capability to use it effectively, the sugar builds up in the blood.

Excessive blood sugar can result in amputation of toes, feet, or legs, blindness, heart problems, kidney failure and stroke.

With respect to figures from the World Health Organization (WHO), the number of individuals globally with diabetes has risen from 108 million in 1980 to 422 million in 2014.

Rates of diabetes have been increasing quicker in middle- and low-income nations. The WHO approximate that by 2030, diabetes will be the 7th leading trigger of death globally.

Human insulin ‘clunky’ in comparison

For their research, Mike Lawrence and colleagues applied the Australian Synchrotron to evaluate the 3-D structure of the cone snail venom insulin protein.

Prof. Lawrence, a specialist in the research of insulin – and how they get into cells via gateways guarded by receptors – describes their fascinating discovery:

“We identified that cone snail venom insulins work quicker than human insulins by preventing the structural modifications that human insulins go through in order to function – they are basically prepared and ready to bind to their receptors.”

Human insulin is “clunky” in comparison with the way the snail venom insulin works, he adds.

Commenting on their study Lawrence said,

Human insulin consists of an extra element that serves as a “hinge” that has to open prior to the molecule can execute the “handshake” with the cell receptor to be able to enter.

However, when they examined the 3-D structure of the snail venom insulin, the study team identified a way to eliminate the hinge from the human insulin. This could accelerate communication with the receptor and assist the insulin enter the cell much more rapidly.

Fast-acting insulin immobilizes prey

The study develops on previous work that identified the marine cone snail uses insulin venom to catch its prey. The snail uses the venom to immobilize unaware fish that swim into its hidden trap.

The insulin that contains venom puts the fish into a state of hypoglycemic – reduced glucose – shock.

Dr. Helena Safavi-Hemami, supervised the study together with Prof. Lawrence.

She states that they were curious to find out how the insulin in the snail venom acts so rapidly, and then that it held the key to making human insulin much more effective.

“We were pleased to find that the principles of cone snail venom insulin could be used to a human setting.”

The investigators identified that cone snail venom insulin “strongly binds the human insulin receptor and triggers receptor signaling.”

“The next phase in our study, which is currently ongoing, is to apply these results to the design of novel and better solutions for diabetes, giving sufferers access to faster-acting insulin.”