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Understanding insulin’s ‘on’ switch

Project summary

Insulin-producing cells in our pancreas have a molecule on their surface, called GLP-1R, which instructs them to release insulin. Some people have a change in their GLP-1R gene which makes GLP-1R do its job better. Dr Tomas and her PhD student will study this genetic change in detail to understand how it helps our pancreas to make more insulin and how it could protect against type 2 diabetes and its complications.

Background to research

In type 2 diabetes, insulin-producing beta cells in the pancreas stop being able to make enough insulin.

Beta cells have a molecule on their surface called a ‘receptor’, which pick up messages from around the body and then acts like an on-off switch for particular activity inside the cell. A receptor called GLP-1R tells the cell to release more insulin. Because of this, lots of type 2 diabetes drugs mimic the action of GLP-1R to help people with type 2 diabetes lower their blood sugar levels.

We all have genes that contain instructions which tell our cells to make GLP-1R. But scientists have discovered that some people have a particular change in their GLP-1R gene that makes GLP-1R more effective. The genetic change also appears to protect them against both type 2 diabetes and heart disease – a common complication of diabetes.

Research aims

Dr Alejandra Tomas will work with a PhD student to discover how this genetic change behaves and how it helps to protect against type 2 diabetes.

They’ll use specialised microscopes to find out if the genetic change leads to a change in where GLP-1R is located on the surface of beta cells, which could help the receptor to pick up and transmit signals more easily.

They will also study beta cells grown in the lab and mice with the ‘protective’ GLP-1R gene to study in detail how it helps to stimulate insulin production and prevent type 2 diabetes.

Potential benefit to people with diabetes

Growing our knowledge of how genetics can affect the important GLP-1R receptor could help scientists to develop new drugs that help to ‘switch on’ insulin production. In turn, this could help to prevent type 2 diabetes, and protect people with the condition from heart disease.

This project has been supported by the Masonic Charitable Foundation.
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