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Cracking genetic codes of type 2 diabetes and depression

Project summary

People with type 2 diabetes are more likely to develop depression. This could in part be down to our genes. Professor Prokopenko plans to study changes in the GLP-1R gene and look at if, and how, the gene could increase the risk of both type 2 diabetes and depression. If the shared genes affect the development of both conditions it could lead to improved medications that work to treat them. 

Background to research

People with type 2 diabetes are more likely to experience depression, and people with depression have a higher risk of getting type 2. Researchers think this could be because some of the same genes can contribute to both conditions.  

One gene that researchers think could play a role in both conditions is called glucagon-like peptide-1 receptor (GLP-1R). The GLP-1R gene makes a protein that sits on insulin-making beta cells. The protein receives messages from the gut when glucose (sugar) is on its way. This tells the beta cells to release insulin to help control blood sugar levels.  

We know that different people have different versions of the GLP-1R gene. These are called gene variants. Professor Prokopenko’s research suggests that some of these different gene variants affect how the protein works and, in turn, affect blood sugar levels. 

Research aims

Professor Prokopenko now wants to understand more about how GLP-1R gene variants affect the risk of type 2 diabetes and depression. First, the researchers will study GLP-1R variants in the lab and look at the shape of the protein they produce, to help understand why some variants work better than others.  

Next, they will link their results with data from very large genetic studies, involving hundreds of thousands of people. This will allow them to discover if any variants are linked with a risk of type 2 diabetes and depression. They will then run experiments that will help to unravel ‘cause and effect’ to work out whether having a GLP-1R variant that works less well increases the risk of developing the conditions.   

Finally, Professor Prokopenko will investigate how different GLP-1R variants affect how well drugs that act on GLP-1R, which are already used to treat type 2 diabetes, work for different people.  

Potential benefit to people with diabetes

This research will give us vital information on the links between GLP-1R genes, type 2 diabetes, depression and how different people respond to different drugs. 

At least 1 in 5 people with type 2 diabetes experience depression. Not only can depression have a dramatic impact on people’s quality of life, but it can also increase the risk of developing diabetes complications. This project could bring to light drugs that could be used to treat both type 2 diabetes and depression together. 

It could also lead to ‘personalised’ type 2 diabetes treatment, allowing doctors to be able to choose the best medications for each individual person, depending on their genetic variants. 

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