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How is the immune system linked to insulin resistance?

Project summary

A part of the immune system – called the complement system – is linked to obesity and type 2 diabetes. Professor Hari Hundal wants to understand this link in more detail, by studying the role of a protein that controls this system. He wants to know if stopping the protein from working could help the body to use insulin and burn fat. This could lead to new treatments to prevent type 2 diabetes and treat insulin resistance in people with the condition.

Background to research

We have a set of proteins circulating in our blood that help our immune system to fight infection and destroy invading bacteria and viruses. It’s called the complement system.

New evidence suggests that obesity can cause this system to become overactive, and this in turn might lead to insulin resistance – a key feature of type 2 diabetes. Insulin resistance is when your body doesn’t respond properly to the insulin that you produce, so glucose can’t move from your blood into your cells. But exactly how obesity and insulin resistance are linked to the complement system isn’t fully understood.

The complement system is controlled by proteins, called complement receptors, which sit on the surface of cells. Professor Hundal has found that one particular complement receptor (called C5aR) lives in muscle. And that boosting the activity of C5aR improves the way muscle cells respond to insulin, so that the cells can better take up glucose from the blood.

Research aims

Professor Hundal wants to understand more about what C5aR does in muscle. He will study muscle cells grown in the lab and from mice to look at how C5aR affects insulin resistance and how the body uses energy from food. This will help the researchers work out, at a molecular level, precisely how the complement system is linked with obesity and type 2 diabetes.

The team then want to see whether targeting C5aR could help people with or at risk of type 2 diabetes lose weight and improve how their bodies respond to insulin. They will use state-of-the-art imaging technology to investigate how blocking C5aR in mice effects how well insulin works, how muscles burn fat and weight gain. 

Potential benefit to people with diabetes

This research will tell us more about the role a specific part of the immune system plays in the development of obesity and type 2 diabetes. In the future, this could lead to new treatments that prevent people from developing type 2 diabetes, and treat insulin resistance for people living with the condition.

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