Researchers at MIT successfully tested an engineered “smart insulin” on mice that reacts to blood sugar levels.
“To make insulin that is glucose responsive is something that we believe will significantly improve blood sugar control in people with diabetes,” said Matt Webber, a post doctoral fellow at the Massachusetts Institute of Technology, who was part of the ten-person team that formulated the new insulin.
To create an insulin that is reactive to blood glucose levels, researchers at MIT attached a molecule containing a chemical group that binds to glucose to commercially available insulin, Webber said. The hydrophobic molecule, called an aliphatic domain, that was added to the insulin dangles from an insulin molecule, causing the insulin to circulate in the bloodstream for at least ten hours. The team then attached a chemical group called PBA to the insulin that allowed it to “reversibly bind 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,” according to a news release from MIT.
“It was a very challenging problem,” Webber said. “It turns out this was very complicated because insulin is a very complex and unstable substance. Also, we had to engineer it for the time it stayed in the body and the level of interaction the molecule would have to sugar, so that it reacted in such a way that did not cause hypoglycemia. It was a multi-pronged approach to solving several issues.”
It was so complex that researchers are still not completely certain why the aliphatic domain causes insulin to circulate for as long as it does without being activated when it’s not needed. “One theory is that the fatty tail (of the aliphatic domain) may bind to albumin, a protein found in the bloodstream, sequestering the insulin and preventing it from functioning until activated by sugar molecules,” according to the news release.
While he was not certain how much money was invested in funding the research, Webber said the team received several million dollars in grants during the four years it took the team to reach their goal.” The Leona M. and Harry B. Helmsley Charitable Trust; the Tayebati Family Foundation; the National Institutes of Health; and the Juvenile Diabetes Research Foundation funded the research.
The next steps in the process of bringing smart insulin to pharmacies will involve formulating the insulin for production, Webber said.
“That is another complicated step because the insulin a person buys now is not just insulin,” Webber said. “It has other ingredients so that it stays viable in a bottle, so that it has long shelf life, and a host of other components that make it work properly and that allow it to be produced on a large scale.”
Webber said while academic settings are “great for discovery, they’re not geared up for commercial production.” He said the new insulin could be licensed to insulin manufacturers, or MIT could decide to produce it itself. Those decisions have not yet been made, he added.
Webber estimated that making the smart insulin commercially viable could take anywhere from “a few years to a few decades” because of the many variables involved in making that happen.
“Safety is primary in that process,” he said.
One thing that is certain is that the accomplishment represents a significant breakthrough in treating both type 1 diabetes and type 2 (for those type 2 diabetics who use insulin to treat their condition).
“It would be a breathtaking advance in diabetes treatment if (this) technology could accomplish the translation of this idea into a routine treatment of diabetes,” said Michael Weiss, a professor of biochemistry and medicine at Case Western Reserve University, who was not on the research team.