A new type of insulin prevents hypoglycemia during diabetes treatment

On May 23, UCLA bioengineers and their colleagues developed a new type of insulin that helps people with diabetes treat diabetes to prevent hypoglycemia. The therapy is evaluating potential clinical trials that, if successful, may alter diabetes treatment, a study published in PNAS.

Insulin is a naturally occurring hormone in the pancreas. It helps the body regulate glucose, which is consumed through food and provides energy to the body. Diabetes occurs when a person's body does not naturally produce insulin (type 1 diabetes) or does not effectively use the insulin produced (type 2 diabetes). In both cases, the doctor will prescribe a regular dose of insulin to control the disease .

In general, people who need insulin are monitored for blood glucose levels with a blood glucose meter or continuous blood glucose monitoring system, and then the corresponding insulin dose is calculated. In addition, regular intake of carbohydrates is important to maintain normal blood sugar levels. Both of these demands are necessarily influenced by human error, and human error can have potentially devastating consequences.

When blood sugar is too low, excess insulin can cause hypoglycemia. This can lead to seizures, coma, and even death in extreme cases.

To be on the safe side, the UCLA-led research team developed a "smart" insulin called i-insulin that prevents blood sugar levels from falling too low.

Insulin plays a "critical" role in the body, helping glucose enter the cell from the bloodstream. When insulin attaches to the cell surface, it activates a protein in the cell called a glucose transporter that then enters the cell surface. This molecule then carries the surrounding glucose from the blood into the cell.

The team added additional molecules to insulin to make new smart insulin. This added molecule, called a glucose transporter inhibitor, chemically blocks the glucose transporter molecules from reaching the surface. Its presence does not prevent all glucose from entering and does not permanently block transport molecules. Instead, this is part of a dynamic process, depending on how many inhibitors and glucose molecules are present.

"Our new insulin is like a 'smart' key," said Dr. Gu Yu, a researcher at the University of California, Los Angeles, and a professor of bioengineering at the University of California, Los Angeles. "Insulin allows glucose to enter the cell, but when blood sugar is normal, the added inhibitor molecules prevent excess glucose from entering the cell. This keeps blood sugar at a normal level and reduces the risk of hypoglycemia."

"This i-insulin can also respond quickly to high sugar levels," added Wang Jinqiang, a joint lead author of the study and a postdoctoral researcher at Professor Gu's research group. "For example, after a meal, when blood sugar levels rise, the level of insulin in the blood rises rapidly, which helps normalize blood sugar levels."

The University of California-led research team tested this smart insulin in mice with type 1 diabetes. After the first injection, insulin i controls blood glucose within the normal range for up to 10 hours. The second injection three hours later extended the protection against hypoglycemia.

"The next step is to further evaluate the long-term biocompatibility of this modified insulin system in animal models before conducting clinical trials," said research collaborator Dr. John Buse, director of the Diabetes Care Center at the University of North Carolina at Chapel Hill School of Medicine. Said. If this desire is realized, it will be one of the most exciting developments in the field of diabetes treatment. "

Professor Gu said: "The new insulin has the potential to optimize response time and how long it can last in the body. It can also be delivered by other means, such as skin patches that automatically monitor blood sugar levels, or pills."

Reference: Zhen Gu et al. Glucose transporter inhibitor-conjugated insulin systems hypoglycemia, Proceedings of the National Academy of Sciences (2019). DOI: 10.1073/pnas.1901967116