'Smart insulin' could be used to treat type 1 diabetes

Behind the Headlines

Tuesday February 10 2015

People with type 1 diabetes have to frequently monitor their blood glucose levels

Type 1 diabetes occurs when the body cannot produce insulin

The Guardian today reports that “smart insulin” may ease the burden on type 1 diabetes  a condition that means the body cannot produce insulin.

This means that those with the condition require frequent insulin shots to stabilise their blood glucose levels. However, this can be a difficult balancing act, as glucose levels can fluctuate throughout the day. Fluctuations can also be potentially dangerous, as they can lead to complications such as hypoglycaemia (low blood glucose).

This was an animal study looking into the development of a new type of “smart insulin” that contains a “molecular switch”, allowing it to directly respond to blood glucose levels, to bring them under control.

When injected into diabetic mice, it was able to normalise their blood glucose levels when they were given glucose challenges (where mice are given a sugary drink) even as long as 13 hours after the initial injection. This suggested that the modified insulin could help with blood glucose control and have a long duration.

Though promising, this research is in the very early stages. This modified insulin has so far only been tested in mice. It is far too early to know whether there could be a new insulin treatment available for type 1 diabetes.   


Where did the story come from?

The study was carried out by researchers from Massachusetts Institute of Technology in the US, and was funded by donations from the Leona M. and Harry B. Helmsley Charitable trust and the Tayebati Family Foundation. The study was published in the peer-reviewed journal PNAS.

The Guardian put a generally positive spin on the results, outlining the potential benefits the new insulin might bring to people with diabetes. It did well in mentioning that the research was done on mice. However, it didn’t really say or discuss why this was an important limitation of the research. While mice share many of our biological traits, we can never be sure that a drug that works in mice will work in humans (or be safe).

Only at the end of the piece was a note of caution introduced. This came from Dr Richard Elliott, of Diabetes UK, who said: “Years of further research and clinical trials will be needed to find out if a similar drug could be used safely and effectively by people with diabetes”.

BBC News’ reporting of the study was less optimistic, as they were quick to mention that “it will take years of testing before treatments could become a reality for patients”.


What kind of research was this?

This was an animal study that looked at developing a type of insulin that is tailored to the individual.

Type 1 diabetes is a condition where the body’s immune system destroys the insulin-producing cells of the pancreas, making the person reliant on life-long insulin injections. There are currently various types of insulin, ranging from some that act quickly and have a short-lasting effect, to those that have a much slower onset and last for longer periods. The type or combination of insulin preparations used will vary considerably from one individual with type 1 diabetes to another.

However, most people will experience difficulty at some point in their insulin treatment, such as problems controlling their blood glucose levels. This means they are potentially at risk of complications such as glucose becoming dangerously low (hypoglycaemia) or high (hyperglycaemia).

In this study, the researchers aimed to prepare a type of insulin that has a “molecular switch” that switches it on or off, depending on glucose levels. They tested it in mice. It is hoped that this treatment could one day give more targeted insulin therapy with better glucose control.


What did the research involve?

The research team prepared their modified insulin, which contains two small chemical molecules bound to insulin. One of the molecules (phenylboronic acid, PBA) is a “glucose sensor”, while the other molecule (an aliphatic domain) helps to give it a long “half-life” so it has similar duration in terms of action to long-acting insulin.

The researchers then tested this new insulin treatment in a mouse model of type 1 diabetes (mice that had been given a treatment to destroy their insulin-producing cells). The mice fasted overnight and were then given injections of the modified insulin at different doses, combined with glucose challenges (given a sugary solution to simulate eating a meal). Blood glucose levels were continuously monitored throughout the tests.

The main analysis compared the glucose control achieved with the new insulin to that achieved using standard insulin injections, all using diabetic mice. They also compared the effects of their insulin with glucose challenges given to healthy, non-diabetic mice.


What were the basic results?

Briefly, the researchers found that their treatment was successful when given to mice with type 1 diabetes. It rapidly normalised their blood glucose levels following the glucose challenge and also demonstrated longer-term effects. In some tests, the modified insulin was able to normalise blood glucose levels in glucose challenges given up to 13 hours after the initial injection.

Their “best-performing” insulin was also demonstrated to give better blood glucose control than standard long-acting insulins. When given a glucose challenge, the diabetic mice given the modified insulin were also able to normalise their blood glucose levels in a similar way to healthy non-diabetic mice.


How did the researchers interpret the results?

The researchers say their study is the first of their knowledge to have demonstrated the effects of a modified insulin molecule in a live animal model. They say that this approach to insulin modification “could afford both long-term and glucose-mediated insulin activity, thereby reducing the number of administrations and improving the fidelity of [blood glucose] control”.



This animal study has demonstrated promise for a modified insulin molecule that contains a “molecular switch”, allowing it to respond to blood glucose levels. When injected into diabetic mice, it was able to normalise their blood glucose levels in response to glucose challenges, sometimes many hours after the initial injection.

This suggested, as the researchers hoped, that the modified insulin could give targeted blood glucose control, and also have a long duration of action, similar to current long-acting insulins.

The researchers hope that this could one day lead to the development of an insulin treatment for people with type 1 diabetes that would give better blood glucose and reduce the risk of complications such as hypoglycaemia.

Though promising, this research is in the very early stages, having only been tested in mice. There are many more developmental hurdles to pass before this innovation could be a new treatment for people. The first stage would be seeing whether the treatment could be developed for testing in humans, then seeing whether it is safe, then gradually conducting trials in successively larger numbers of people. This will determine whether it is safe and effective compared with other insulins used by people with type 1 diabetes.

While it is perfectly fine to be optimistic, there are no guarantees. Promising research in mice does not necessarily lead to effective treatments for humans.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

'Smart' insulin may ease burden of type 1 diabetes patients, research suggests. The Guardian, February 9 2015

'Smart' insulin hope for diabetes. BBC News, February 10 2015

Links to the science

Chou D, Webber MJ, Tang DC, et al. Glucose-responsive insulin activity by covalent modification with aliphatic phenylboronic acid conjugates. PNAS. Published online February 9 2015


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Media last reviewed: 25/04/2015

Next review due: 25/04/2017

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