A UCLA-led research team recently developed a modified form of insulin that could help prevent dangerous drops in blood sugar in diabetic patients. The treatment showed efficacy in animal models and could improve safety in diabetic care if found to be effective in clinical trials. These findings were published in the Proceedings of the National Academy of Sciences.
Overview of Insulin
Insulin functions to lower one’s blood sugar by promoting glucose uptake from the blood. In healthy individuals, the insulin hormone is secreted after consuming food in response to elevated blood sugar. When insulin adheres to a cell’s surface it triggers the glucose transporter protein to migrate to the cell membrane, where the transporter brings surrounding glucose from the blood into the cell. This natural process is the body’s way of maintaining blood sugar.
What is Diabetes
Diabetes is a condition that either occurs when the body does not properly produce insulin or does not respond properly to the hormone. These cases define Type 1 and 2 diabetes, respectively, and both conditions are typically managed through insulin injections to regulate blood sugar. If one injects too much insulin, they may experience abnormally low blood sugar levels, known as hypoglycemia. Hypoglycemia is a potentially dangerous condition that can result in coma, seizures, and fatality.
Bioengineers from UCLA and their colleagues have recently developed a “smart” insulin, known as i-insulin, to prevent hypoglycemia. The team modified the insulin molecule to contain a glucose transporter inhibitor, which blocks the glucose transporter molecule on the surface of cells. This inhibitor function depends on the quantity of glucose and inhibitor present and does not block all glucose transport.
“Our new i-insulin works like a ‘smart’ key,” said the principal investigator Zhen Gu, a bioengineering professor at the UCLA Samueli School of Engineering. “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.”
“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,” Gu said. “And it could be delivered in other methods, such as a skin patch that automatically monitors blood sugar levels, or in pills.”
Other collaborators included lead author Jicheng Yu, chief scientific officer of Zenomics and a former doctoral student in Gu’s lab, UCLA bioengineering postdoctoral scholars Zejun Wang and Jun Fang, and UCLA professors Julian Whitelegge and Song Li.
In a study involving mouse models of Type 1 diabetes, the i-insulin treatment was found to control blood sugar within the healthy range for as long as 10 hours after injection. In addition, the team found a second injection three hours later prolonged this prevention of hypoglycemia.
The researchers have filed for a patent on the i-insulin treatment, and plan to conduct more research before eventually reaching the clinical trial stage.
“The next step is to further evaluate the long-term biocompatibility of the modified insulin system in an animal model before determining whether to move to clinical trials,” said co-author Dr. John Buse, director of the Diabetes Care Center at the University of North Carolina at Chapel Hill School of Medicine. “The vision, if realized, would be one of the most exciting advances in diabetes care.”
— ClearCritique (@CritiqueClear) May 17, 2019