Science Interviews

Interview

Tue, 17th Feb 2015

Smart insulin: a diabetes game changer?

Dr Matthew Webber, Massachusetts Institute of Technology

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For people with type 1 diabetes, whose pancreas doesn't make enough of the Diabetesglucose-regulating hormone insulin, life is dominated by pricking fingers to measure blood sugar levels, and injections of insulin. But what if this injected insulin could be made smarter, circulating in the body until the exact time it's needed, only springing into action after a meal? It sounds too good to be true, but now, publishing in PNAS, MIT scientist Matthew Webber has made it happen, at least in mice, as he explains to Kat Arney...

Matthew - The idea was to try to make insulin a little bit more autonomous, if the insulin molecule itself could remain in the body but not be functional unless it was needed. So, if blood glucose levels go up as a result of a meal, then the insulin could turn on and become active versus the patient having to kind of know when their blood glucose level was high and inject themselves.

Kat - Describe to me a bit more about this particular insulin. What does it look like and how does it work?

Matthew - So, the vision for the insulin or at least how we anticipate it to work is that the small molecule that weve attached to the insulin protein itself would enable the insulin to become sequestered within the body and be inactive.

Kat - So, it would hide away when its not needed?

Matthew - Right. So yeah, it would remain sequestered and hide until it was needed.

Kat - And then what happens when someone say, has a dinner and their blood glucose starts to go up?

Matthew - The general idea we tried to simulate in a mouse was a meal. So, we inject glucose to simulate a meal and then the insulin in theory will turn on and will become active and ready. And then will result in a reduction of blood glucose levels, the way insulin is supposed to normally work in a healthy functioning pancreas.

Kat - So explain a little bit more about how does the glucose actually make this clever insulin come out of hiding? How does that work?

Matthew - So, the mechanism is not entirely clear to us.

Kat - Even though you built it?

Matthew - Even though we built it, yes. So, we had an envisioned mechanism in mind which was that it would bind to a protein that is in very high concentration in the blood which would make it inactive. And then in the presence of glucose, it would reduce the binding of this protein and then it would become more active. We werent able to verify that mechanism in situ in a test tube but that doesnt necessarily mean the mechanism isnt working that way when its in the body when you get into the complex physiologic environment of the body, a lot can change.

Kat - But I guess the key thing and for anyone whos listening who is affected by type 1 diabetes is going to be: Does it work? And how soon is it going to be here?

Matthew - Right. So, does it work? It works in mice. Some of our studies demonstrate that it works as well as a healthy pancreas which is really the ultimate gold standard for glucose control. That's the way a healthy person would control their glucose. So, it works in mice. As far as moving forward, were currently in negotiations with some pharmaceutical companies and some other people that might have interest in helping us to advance this clinically. And hopefully, that's a process that can begin in the coming months and years before well actually know for sure if its working well in the human setting.

Kat - Assuming that all goes well in the further tests and eventually taking it into humans does go well, how do you envisage it working? Would someone say, take it once a week?

Matthew - So, the idea I think would be that a person would maybe take this once a day. I think it would kind of serve to provide a basal level of insulin in the body that could become activated to help with some of the glycaemic control issues that diabetics often experience.

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