News

Five promising research ideas for novel insulins

June 22, 2023

Last month, we held a symposium on novel insulins, where experts from around the world met virtually to discuss their ideas for how to develop the next generation of insulins. Their fascinating discussion will be published in a scientific review paper later this year. In the meantime, here is a preview of five of the most exciting ideas that were discussed at the symposium.

1. Fast-acting insulin inspired by snails

We all know how dangerous it is to take too much insulin – and now we’ve found out that even snails understand this. A type of underwater snail called the cone snail uses insulin as a weapon to immobilise their prey. There are subtle differences in this snail’s insulin, which allow it to act much faster than the insulin that people with type 1 currently use. So, diabetes researchers have been teaming up with zoologists to design a super-fast-acting insulin for humans.

A cone snail attacking a fish

A cone snail attacking a fish

Because insulin is such a big molecule, it can take a while to act. Scientists have been trying to make insulin smaller without losing any of its function, but they haven’t been successful yet. Now, researchers including Professor Daniel Chou from Stanford University are trying to mimic the chemical structure of cone snail insulin venom and tweak it slightly to improve its effectiveness in people.

If these researchers manage to create this smaller version of insulin, our skin should be able to absorb it much faster than current insulins. Ultra-fast insulins like this would reduce the time you need to wait between injecting and eating and also offer hope for fully closed loop systems, which don’t require a person to give warning of meals and exercise.

2. Oral insulin pill inspired by tortoises

The problem with taking insulin orally in a pill also partially comes down to its size. If you were to swallow a pill of insulin, it would first break down in your stomach, meaning it couldn’t work properly, and even then, it would still be too big to pass through your intestines. But world-renowned scientist Professor Robert Langer at Massachusetts Institute of Technology (MIT) has developed an ingenious pill that protects insulin and then fires it into the stomach lining.

A diagram of Professor Langer’s insulin pill design

A diagram of Professor Langer’s insulin pill design

The clever design features a tiny spring which propels an arrow of insulin directly into the stomach lining. This happens about an hour after you swallow the device, which is packed inside a biodegradable case, to allow time for it to reach the stomach. But how do you make sure the insulin is always fired into the stomach wall? That’s where the tortoises come in.

A species called the leopard tortoise is self-orienting, which means that it always stays upright. No matter how the tortoise falls or rolls, it will always end up on its feet. This clever trick is due to how its weight is distributed. Inspired by these tortoises, Professor Langer distributed the weight in his insulin pill in the same way so that it always lands with the insulin pointed down.

His pill is called SOMA (self-oriented medical applicator) and Novo Nordisk has so far tested it in 65 people with type 1 diabetes and found no bad side effects.

A leopard tortoise

A leopard tortoise

3. A weekly insulin could be coming

People with type 1 currently take a type of slow-acting insulin, known as basal insulin, once or twice a day to control blood sugar outside of eating. Researchers are developing a new generation of insulins that can work for even longer, reducing the number of injections you need. It may seem counterintuitive, but by editing insulin to make it less effective at clearing glucose, researchers can make it work for longer. This reduced function means it can stay in the body without causing hypoglycaemia.

Novo Nordisk have used this principle to create an insulin called insulin isodec, which has had very promising results in clinical trials. The company has now applied to the US Food and Drug Administration (FDA) for regulatory approval, meaning weekly basal insulin injections could soon become a reality for people with diabetes.

4. Ways to make insulin respond to glucose

Scientists specialising in different disciplines from chemistry to bioengineering have inventive ideas about how to create glucose-responsive insulins, also known as smart insulins. An interesting idea is to create a mixture of insulin and a chemical that can sense glucose, with a large molecule to keep them together.

A team led by Professor Matthew Webber at the University of Notre Dame has developed such a mixture. The insulin mixture is an insoluble blob at a neutral pH, which means not acidic or alkaline. Then, when glucose levels rise, the pH becomes more acidic and the mixture dissolves, releasing the insulin so that it can bind to glucose. Their tests on animals have shown that a single dose of their smart insulin mixture can keep glucose levels stable for up to five days in mice and up to a week in pigs.

The glucose-responsive insulin mixture in its soluble state and its insoluble state

The glucose-responsive insulin mixture in its soluble state and its insoluble state

5. Computer models to streamline research

Treatments must be tested in animals before they can enter clinical trials with people. But lots of drugs that are effective in animals turn out not to work in humans. Professor Michael Strano and his team at MIT have developed a sophisticated computer model of the glucose control system in animals and humans, which can predict how the body will respond to different treatments. The team created the simulation using a combination of maths, biochemistry and extensive data collection from people with type 1.

Researchers can plug their drug designs into the computer model to predict whether it will work or not and edit their designs accordingly. This tool is especially useful for glucose-responsive ‘smart’ insulins because scientists all over the world are experimenting with a range of different approaches to develop them. The simulator will streamline the research process by allowing researchers to only invest time and energy in their ideas that have the best chance of success. It will save crucial time, money and effort in the research and development stage and ensure only the insulins (and other therapies for type 1) with the most potential progress to clinical trials.

Bonus: glucose-responsive glucagon

We can apply all of these ideas for creating glucose-responsive insulin to the hormone glucagon, which has the opposite effect to insulin. Glucagon stimulates glucose production and release from where it is stored in the liver, which is why it is a treatment for severe hypoglycaemia.

A glucagon emergency rescue kit to treat severe hypos

A glucagon emergency rescue kit to treat severe hypos

Dr Alborz Madavi, a researcher who founded the company Protomer, believes that a long-acting dose of glucose-responsive glucagon, which could be taken just once a week, would protect against hypoglycaemia. The smart glucagon would turn on at low glucose levels to prevent hypos and work alongside the user’s normal insulin treatment. Dr Mahdavi believes this would help people with type 1 feel less worried about overnight hypos and allow more flexibility with taking insulin.

Type 1 Diabetes Grand Challenge offers hope for novel insulins

The £15 million set aside by the Type 1 Diabetes Grand Challenge to tackle the challenge of novel insulins will expand upon this exciting research to bring these innovative ideas closer to reality. From hormones that can respond to varying glucose levels, to fast- and long-acting insulin, to easier ways to take insulin without injections, novel insulins are coming, and the Grand Challenge will get us there faster.

Novel Insulin Grand Challenge
Novel Insulin Grand Challenge

While we push towards a cure, we need next generation insulins such as those that can respond to changing blood sugar levels and eliminate highs and lows. Find our more about our Novel Insulin Grand Challenge.

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Novel insulins symposium

Leading experts and researchers from around the world came together to share their progress, challenges and hopes for developing new forms of insulin.

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About us

By harnessing the power of collaboration, targeting research areas with the greatest potential, and stimulating bold, innovative research at scale, we’re creating change that will improve the lives of millions of people with type 1 diabetes.

News, Video

Five promising research ideas for novel insulins

May 19, 2023

1. Fast-acting insulin inspired by snails

We all know how dangerous it is to take too much insulin – and now we’ve found out that even snails understand this. A type of underwater snail called the cone snail uses insulin as a weapon to immobilise their prey. There are subtle differences in this snail’s insulin, which allow it to act much faster than the insulin that people with type 1 currently use. So, diabetes researchers have been teaming up with zoologists to design a super-fast-acting insulin for humans.

______Content of this video______

00:00:00 Introduction to the Novel Insulins Symposium – Professor Simon Heller
00:06:04 Discovery and design of novel insulins – Dr Peter Kurtzhals
00:38:41 Glucose-responsive smart insulin and delivery patch – Professor Zhen Gu
01:09:05 Molecular Engineering of Insulin: Progresses and Challenges – Professor Daniel Chou
01:35:33 Molecular engineering of glucose-responsive insulin – Professor Matthew Webber
02:07:00 Towards oral insulin and an artificial pancreas – Professor Robert Langer
02:26:03 Ultra-stable insulin analogs and their clinical applications – Professor Michael Weiss
02:55:22 Glucose-sensing insulins – Dr Alborz Mahdavi
03:31:42 Diabetes therapeutics from computational design – Professor Michael Strano
03:59:00 Discussion Panel – All speakers
04:36:42 Concluding remarks and next steps – Ms Rachel Connor

News

Five promising research ideas for novel insulins

May 17, 2023

1. Fast-acting insulin inspired by snails

We all know how dangerous it is to take too much insulin – and now we’ve found out that even snails understand this. A type of underwater snail called the cone snail uses insulin as a weapon to immobilise their prey. There are subtle differences in this snail’s insulin, which allow it to act much faster than the insulin that people with type 1 currently use. So, diabetes researchers have been teaming up with zoologists to design a super-fast-acting insulin for humans.

Video, Views

Five promising research ideas for novel insulins

May 11, 2023

1. Fast-acting insulin inspired by snails

We all know how dangerous it is to take too much insulin – and now we’ve found out that even snails understand this. A type of underwater snail called the cone snail uses insulin as a weapon to immobilise their prey. There are subtle differences in this snail’s insulin, which allow it to act much faster than the insulin that people with type 1 currently use. So, diabetes researchers have been teaming up with zoologists to design a super-fast-acting insulin for humans.

News

Five promising research ideas for novel insulins

April 27, 2023

1. Fast-acting insulin inspired by snails

We all know how dangerous it is to take too much insulin – and now we’ve found out that even snails understand this. A type of underwater snail called the cone snail uses insulin as a weapon to immobilise their prey. There are subtle differences in this snail’s insulin, which allow it to act much faster than the insulin that people with type 1 currently use. So, diabetes researchers have been teaming up with zoologists to design a super-fast-acting insulin for humans.

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Professor Simon Heller Chair of the Type 1 Diabetes Grand Challenge scientific advisory panels

Professor Simon Heller is chair of all three scientific advisory panels in the Type 1 Diabetes Grand Challenge, covering beta cells, novel insulins and root causes of type 1 diabetes. Along with the leading experts who sit on these panels, Simon will help to steer the direction of the Grand Challenge to make sure our funding is invested in the right places, with the biggest potential to change the lives of people with type 1 diabetes. He is also Professor of Clinical Diabetes at the University of Sheffield and a world-renowned scientist, whose research has led the way in transforming our understanding of hypoglycaemia.

Why did you want to get involved with the Type 1 Diabetes Grand Challenge?

Simon: “It was a huge honour to be asked to assist in determining how this huge amount of funding could best be used to benefit type 1 diabetes research in the UK. It’s important to me to do my best to see our research move more quickly towards a cure for people with type 1.”

How do you think the Type 1 Diabetes Grand Challenge will be a game-changer for type 1 diabetes research?

“I hope that the Type 1 Diabetes Grand Challenge will allow the UK to play a major part in moving the research landscape closer to a cure. It will hopefully enable us to do something much more rapidly than we otherwise would be able to.”

What would a cure for type 1 diabetes look like to you?

“A cure would be removing the burden of day-to-day self-management of type 1 diabetes. In particular, it would allow people with the condition to live a life of spontaneity and doing activities which those of us without diabetes often take for granted.”

How did you get into the field of type 1 diabetes research?

“When I arrived at the Queens Medical Centre in Nottingham as a trainee registrar, I was intending to be a cardiologist. But a six-month placement in a diabetes team changed that. The legendary diabetes researcher Robert Tattersall (who discovered MODY and introduced the world to self-monitoring blood glucose levels) was my boss. He was a wonderful teacher who taught me to listen to people with diabetes and learn for myself how much it asked of people in terms of self-management. He also showed me that it wasn’t the healthcare professionals who made the biggest impact on managing type 1, but instead how much the person themselves could learn and implement about this very complex condition. Robert inspired me to become a researcher and showed me what an interesting and important specialty diabetes is.”

What has been your career highlight so far?

“It’s hard to narrow it down. One highlight is bringing the DAFNE training course – which helps people with type 1 lead a healthy life – from Germany to the UK’s NHS. Another key achievement was discovering that repeated hypos lead to impaired awareness of hypoglycaemia and increased risk of hypoglycaemia. I feel fortunate that I have been involved in research which has made a difference to the lives of people with type 1.”

Tell us something we don’t know about diabetes or the pancreas

“When I was preparing a talk on hypoglycaemia, I learnt that the first definition of 1 unit of insulin was the amount of insulin which could cause an epileptic seizure in a rabbit. This is because over a hundred years ago when insulin was discovered, there was no way of measuring insulin amounts. I read this fact in a wonderful book by Michael Bliss titled The Discovery of Insulin.”

What are you currently working on?

“My main research project at the moment is working with researchers from the USA, UK and Australia on a large research trial. The study is testing what the most effective way of restoring the warnings for hypoglycaemia in people with type 1 who have lost them.”

What skills do you need to have to be a great researcher?

“From working with great researchers, I’ve learnt that they need to be curious, creative and persistent. The best clinical researchers listen to people with lived experience to ensure they address important questions.”

What do you like doing when you’re not working on research?

“I spend my spare time travelling to interesting places, reading, and listening to music – particularly opera. I also love spending time with my family and my three grandkids. Less rewarding in recent years has been my love for Tottenham Hotspur FC.”

What would you be doing if you weren’t a researcher?

“I can’t think of any other careers as rewarding as supporting patients. I’d be very happy just doing clinical work alone.”

News

Q&A with Professor Simon Heller

We spoke to Professor Simon Heller, world-renowned diabetes specialist and Chair of the Type 1 Diabetes Grand Challenge Scientific Advisory Panels, to find out about his research journey and hopes for the Grand Challenge

November 22, 2022
Professor Simon Heller Chair of the Type 1 Diabetes Grand Challenge scientific advisory panels

Professor Simon Heller is chair of all three scientific advisory panels in the Type 1 Diabetes Grand Challenge, covering beta cells, novel insulins and root causes of type 1 diabetes. Along with the leading experts who sit on these panels, Simon will help to steer the direction of the Grand Challenge to make sure our funding is invested in the right places, with the biggest potential to change the lives of people with type 1 diabetes. He is also Professor of Clinical Diabetes at the University of Sheffield and a world-renowned scientist, whose research has led the way in transforming our understanding of hypoglycaemia.

Why did you want to get involved with the Type 1 Diabetes Grand Challenge?

Simon: “It was a huge honour to be asked to assist in determining how this huge amount of funding could best be used to benefit type 1 diabetes research in the UK. It’s important to me to do my best to see our research move more quickly towards a cure for people with type 1.”

How do you think the Type 1 Diabetes Grand Challenge will be a game-changer for type 1 diabetes research?

“I hope that the Type 1 Diabetes Grand Challenge will allow the UK to play a major part in moving the research landscape closer to a cure. It will hopefully enable us to do something much more rapidly than we otherwise would be able to.”

What would a cure for type 1 diabetes look like to you?

“A cure would be removing the burden of day-to-day self-management of type 1 diabetes. In particular, it would allow people with the condition to live a life of spontaneity and doing activities which those of us without diabetes often take for granted.”

How did you get into the field of type 1 diabetes research?

“When I arrived at the Queens Medical Centre in Nottingham as a trainee registrar, I was intending to be a cardiologist. But a six-month placement in a diabetes team changed that. The legendary diabetes researcher Robert Tattersall (who discovered MODY and introduced the world to self-monitoring blood glucose levels) was my boss. He was a wonderful teacher who taught me to listen to people with diabetes and learn for myself how much it asked of people in terms of self-management. He also showed me that it wasn’t the healthcare professionals who made the biggest impact on managing type 1, but instead how much the person themselves could learn and implement about this very complex condition. Robert inspired me to become a researcher and showed me what an interesting and important specialty diabetes is.”

What has been your career highlight so far?

“It’s hard to narrow it down. One highlight is bringing the DAFNE training course – which helps people with type 1 lead a healthy life – from Germany to the UK’s NHS. Another key achievement was discovering that repeated hypos lead to impaired awareness of hypoglycaemia and increased risk of hypoglycaemia. I feel fortunate that I have been involved in research which has made a difference to the lives of people with type 1.”

Tell us something we don’t know about diabetes or the pancreas

“When I was preparing a talk on hypoglycaemia, I learnt that the first definition of 1 unit of insulin was the amount of insulin which could cause an epileptic seizure in a rabbit. This is because over a hundred years ago when insulin was discovered, there was no way of measuring insulin amounts. I read this fact in a wonderful book by Michael Bliss titled The Discovery of Insulin.”

What are you currently working on?

“My main research project at the moment is working with researchers from the USA, UK and Australia on a large research trial. The study is testing what the most effective way of restoring the warnings for hypoglycaemia in people with type 1 who have lost them.”

What skills do you need to have to be a great researcher?

“From working with great researchers, I’ve learnt that they need to be curious, creative and persistent. The best clinical researchers listen to people with lived experience to ensure they address important questions.”

What do you like doing when you’re not working on research?

“I spend my spare time travelling to interesting places, reading, and listening to music – particularly opera. I also love spending time with my family and my three grandkids. Less rewarding in recent years has been my love for Tottenham Hotspur FC.”

What would you be doing if you weren’t a researcher?

“I can’t think of any other careers as rewarding as supporting patients. I’d be very happy just doing clinical work alone.”