Engineered Insulin

For patients with diabetes, regulating insulin is critical to maintaining normal blood-sugar levels and good health. However, it can be difficult for patients to determine exactly how much insulin they need to prevent their blood sugar from swinging too high or too low.

MIT engineers hope to improve treatment with a new type of engineered insulin. In tests in mice, the researchers showed that their modified insulin can circulate in the bloodstream for at least 10 hours, and that it responds rapidly to changes in blood-sugar levels.

“The real challenge is getting the right amount of insulin available when you need it, because if you have too little insulin your blood sugar goes up, and if you have too much it can go dangerously low,” says Daniel Anderson, an associate professor of chemical engineering and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science.

People with type 1 diabetes lack insulin, which is normally produced by the pancreas and regulates metabolism by stimulating muscle and fat tissue to absorb glucose from the bloodstream.

In collaboration with Institute Professor Robert Langer (see profile), Anderson and colleagues set out to create a new form of insulin that would remain in the bloodstream for a long time but would be activated only when needed—that is, when blood-sugar levels are too high.

Avoiding unnecessary activation of insulin would prevent sugar levels from becoming dangerously low, a condition known as hypoglycemia that can lead to shock and even death.

To create this glucose-responsive insulin, the researchers first added a long chain of fatty molecules, which dangles from the insulin molecule and helps it circulate in the bloodstream longer. They also attached a chemical group called PBA, which can bind reversibly to glucose. When blood-glucose levels are high, the sugar binds to insulin and activates it, allowing the insulin to stimulate cells to absorb the excess sugar.

Mice that received the engineered insulin showed faster responses to injections of glucose than those receiving unmodified insulin or a previously developed type of long-acting insulin that lacks a glucose-sensing component.

Giving this type of insulin, instead of the other long-acting insulin, once a day could offer patients a better alternative that reduces their blood-sugar swings, which can cause health problems when they continue for years and decades, Anderson says.