Model predicts performance of glucose-responsive insulin

People with Type 1 diabetes must check their blood glucose several times a day and inject themselves with insulin to keep their blood sugar levels within a healthy range. A better alternative, long sought by diabetes researchers, would be insulin that is engineered to linger in the bloodstream, becoming active only when needed, such as right after a meal.

One obstacle to developing this kind of “glucose-responsive insulin” is that it is difficult to know how these drugs will behave without testing them in animals. MIT researchers have now created a computer model that should streamline the development process: Their new model can predict how glucose-responsive insulin (GRI) will affect patients’ blood sugar, based on chemical traits such as how quickly the GRI becomes activated in the presence of glucose.

“The concept of GRI has been a longstanding goal of the diabetes field,” says Michael Strano, the Carbon P. Dubbs Professor of Chemical Engineering at MIT. “If done correctly, you could make it so that diabetics could take an occasional dose and never have to worry about their blood sugar.”

The new model allowed the researchers to identify several strong GRI candidates, which they now plan to test in animals.

Strano is the senior author of two recent papers on GRIs, which appear in the journals Nature Chemistry and Advanced Healthcare Materials. The first author of both papers is MIT graduate student Naveed Bakh.

“A rational design”

In recent years, scientists have experimented with several types of GRIs. In the recent Nature Chemistry article, Strano and colleagues outlined some of the progress that has been made and laid out a series of specific synthetic approaches that could help make GRIs a practical reality. These include using mathematical models of the human body to predict how GRIs would behave in patients, making it easier to design and test such drugs.

In the Advanced Healthcare Materials paper, the MIT team used that type of…

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