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Preventing plaque build-up in type 2 diabetes

Project summary

People with type 2 diabetes are at a higher risk of developing heart disease. Dr Matthew Gage is studying how insulin resistance affects the most common cause of heart disease: the build-up of plaques in blood vessels. In turn, this research could help us to find new ways to reduce the risk of heart disease in people with type 2 diabetes.

Background to research

One of the main features of type 2 diabetes is insulin resistance, which usually gets worse with age. Insulin resistance is where cells around the body need much more insulin than usual to work properly and absorb glucose from the blood. 

Immune cells called macrophages are involved in heart and blood vessel disease, as they play a role in clogging up blood vessels. Macrophages change and become resistant to insulin when they get older. A molecule, called SHIP2, plays a role in insulin resistance in cells and it's been thought that reducing SHIP2 activity can restore a cell’s ability to respond to insulin.

But with our funding, Dr Gage found evidence to suggests otherwise. His previous study gave us early evidence that over the longer term, reducing SHIP2 could in fact make cells more resistant to insulin. And Dr Gage believes that it could be beneficial to do this, because old and insulin resistant macrophages may be less able to clog up blood vessels. 

Research aims

Dr Gage wants to study the impact of reducing the amount of SHIP2 in macrophages in mice to better understand its impact on the risk of heart and blood vessel problems. He and his team will investigate what happens when the amount of SHIP2 is reduced in macrophages, but not in other types of cells. They want to find out how macrophages behave on their own, and how lowering SHIP2 levels affects the heart and blood vessels. 

This will help the researchers to understand if insulin resistance in macrophages is a good thing, and how drugs that target SHIP2 should be directed to help reduce the risk of heart attacks and stroke.

 

Potential benefit to people with diabetes

People with type 2 diabetes are at a higher risk of developing heart problems, so we need to find ways to reduce this risk. If successful, this research could open doors to developing new drugs that reduce plaque build-up in blood vessels and protect against heart disease.
 

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