New type of insulin could prevent hypoglycemia in diabetics

By Sally Robertson, B.Sc.May 17 2019

Researchers at the UCLA Samueli School of Engineering have created a new type of insulin that could prevent hypoglycemic episodes among people who use the hormone to manage their diabetes.

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The drug is now being assessed for its potential use in clinical trials and if it is found to be effective, the treatment could change diabetes management.

Insulin is a hormone produced by the pancreas that helps to control blood glucose levels when food is eaten. Diabetes arises either when the pancreas does not produce insulin (type 1 diabetes) or when the body fails to use the insulin that is produced effectively (type 2 diabetes). The condition affects more than 400 million individuals globally.

Both forms of diabetes can be managed through regular doses of insulin and people taking the drug generally monitor their blood sugar level using a glucose meter or continuous glucose monitoring system that calculates the doses of insulin that are needed. People with diabetes also need to ensure they have a regular intake of carbohydrates to maintain a healthy blood glucose level.

Both the glucose monitoring and the carbohydrate intake are management approaches that are subject to human error, which can have potentially dangerous effects. Taking too much insulin can lead to dangerously low blood sugar levels (hypoglycemia), which can result in seizures, coma and in severe cases, death.

As reported in the Proceedings of the National Academy of Sciences, the UCLA researchers have now developed a new form of insulin that ensures blood glucose does not fall too low.

Within the body, insulin helps glucose to access blood cells by attaching to the cell surface and activating a glucose transporter protein within the cell that then moves towards the cell’s surface. The transporter then draws nearby glucose from the bloodstream into the cell.

What the UCLA researchers have now done is to add a glucose transporter inhibitor to insulin, which blocks the glucose transporter once it reaches the cell surface. The inhibitor does not completely stop glucose being brought into the cell, nor does it completely block the transporter; rather, it acts in a dynamic manner, allowing glucose to enter depending on the number of inhibitor and glucose molecules present.

Principal investigator Zhen Gu describes the new insulin as working like a “smart” key:

The insulin lets glucose get into the cell, but the added inhibitor molecule prevents too much from going in when blood sugar is normal. This keeps blood sugar at normal levels and reduces the risk of hypoglycemia."

Zhen Gu, Principal Investigator

Co-lead author Jingiang Wang says the new insulin also a rapidly responds to the presence of too much glucose, with its level quickly increasing in the blood after a person eats to normalize the rising glucose level.

When the researchers tested the insulin in a mouse model, the drug maintained a normal glucose level for up to 10 hours after first injection and for a further three hours after a second injection.

Next, the team plans to assess the long-term biocompatibility of the new insulin in an animal model, before deciding whether to move forwards with clinical trials.

"The vision, if realized, would be one of the most exciting advances in diabetes care," says co-author John Buse.

"The new insulin has the potential to be optimized for response times and how long it could last in the body before another dose would be required. And it could be delivered in other methods, such as a skin patch that automatically monitors blood sugar levels, or in pills,” says Gu.