Diabetes: What are the new research projects in the field of “smart” insulin? | Commentary

The story so far: The Type 1 Diabetes Grand Challenge, a partnership between the Steve Morgan Foundation, Diabetes UK and JDRF, announced more than £2.7 million in grants for new research into developing next-generation insulin to manage type 1 diabetes on Monday, 12 August 2024. The funding will accelerate research into insulin that mimics the work of a healthy pancreas, the initiative says.

What is Type 1 Diabetes?

Type 1 diabetes is a chronic disease characterized by insufficient insulin production, requiring frequent insulin doses, often daily, sometimes multiple times a day. Without insulin, glucose continues to build up in the bloodstream, causing hyperglycemia. The insulin hormone helps regulate blood sugar levels by allowing glucose to enter cells and be used to make energy.

More about the grant

The funding will support six new international research projects focused on developing next-generation or novel insulins, to be carried out at universities in the US, Australia and China.

“The six new funded research projects address a major shortcoming of insulin therapy. Minimizing the risk of hypoglycemia by combining insulin with glucagon would alleviate one of the major concerns associated with insulin therapy today. If successful, these research projects will therefore herald a new era of insulin therapy,” said Tim Hines, Vice Chair of the Type 1 Diabetes Grand Challenge's Novel Insulins Scientific Advisory Board.

According to the Type 1 Diabetes Grand Challenge, four of the newly funded projects relate to glucose-responsive insulin (GRI), which can respond to changes in blood sugar levels.

GRI is activated when blood glucose levels exceed a certain level and inactivated when blood glucose levels fall below a certain level, which is expected to prevent both hyperglycemia (high blood glucose levels) and hypoglycemia (low blood glucose levels).

Another research project is focused on developing short-acting insulin. Even the fastest-acting types of insulin currently available have a delay between when the drug is taken and how it affects blood sugar levels, which can cause blood sugar to spike before the insulin can lower it, putting patients at risk.

The final funded project focuses on the combination of insulin and glucagon.

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Glucagon is also secreted by the pancreas to raise blood sugar levels and prevent them from falling below dangerous levels. The project is based on the concept that combining both insulin and glucagon in one formulation can stabilize blood sugar levels.

GRI Project

The four GRI projects are being researched at Monash University in Australia, Wayne State University in the US, the Jinhua Institute at Zhejiang University in China, and the University of Notre Dame in the US.

The Monash University project involves developing a second-generation nanosugar insulin system based on advanced nanotechnology. In experiments with the first generation of this insulin delivery system, insulin and tiny glucose-sensing molecules called nanosugars are injected subcutaneously. These nanosugars respond to very small changes in blood sugar levels and release insulin without patient intervention only if blood sugar levels go out of range. The aim of the experiment is to reduce the number of times people with type 1 diabetes have to inject insulin.

Researchers at Wayne University are working on developing “smart insulin” that can sense changes in blood sugar levels and respond by releasing the right amount of insulin at the right time. Chemical engineer Zhiqiang Cao's team plans to develop a smarter insulin that is “more” sensitive to changes in blood sugar levels because some of the new insulins are not as potent as currently available insulins, requiring higher doses to have the same effect on blood sugar levels.

The third project, conducted by researchers at the Jinhua Institute of Zhejiang University in China, involves a new insulin that responds immediately to rising blood glucose levels. This new insulin forms a reservoir of insulin under the skin when injected, so it can be used daily or weekly. The experiments start with an insulin/polymer complex and then add a safe glucose-sensing molecule. In this project, the team will refine the GRI to ensure all the components work together effectively. The next step will be to ensure the GRI can properly release insulin from the reservoir, especially when blood glucose levels are high.

Researchers at the University of Notre Dame in the US have developed a smart insulin delivery system using microparticles called insulin-containing nanocomplexes that can be injected subcutaneously to create a reservoir and automatically release insulin when blood sugar levels rise. The project will be further developed and tested in pigs exposed to real-life scenarios.

Ultrafast Insulin

Scientists at Stanford University in the US are developing and testing a fast-acting form of insulin that would work only when needed and reduce the risk of highs and lows in blood sugar in people with type 1 diabetes.

Current fast-acting insulin is a collection of six molecules that must be separated to form a single insulin molecule in order to regulate blood sugar levels. Even these single molecules can pair up and clump together, preventing blood sugar regulation. The new research will focus on designing an insulin molecule that doesn't clump together and acts quickly in the bloodstream. The design is based on an insulin molecule found in the venom of conus snails, a type of marine snail that uses insulin as a weapon.

Insulin + glucagon

The Indiana University research team will combine insulin and glucagon in their project to prevent blood sugar levels from rising and falling too quickly. The molecule was tested in rats with type 1 diabetes and found to reduce the risk of hypoglycemia at mealtimes and throughout the day. The experiment will also test the stability of the molecule and explore different ways of manufacturing it.