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Investigating the ins and outs of insulin

Project summary

Insulin helps fat and muscle cells to take in glucose from the bloodstream, so they can use it for fuel. Professor Gwyn Gould wants to understand, on a molecular level, exactly how this process works and how it goes wrong in people with Type 2 diabetes. This knowledge will help lead the way to new future treatments that prevent this from happening.

Background to research

We need insulin to keep our blood glucose levels constant, as it allows fat and muscle cells to take in glucose from our bloodstream. For this to happen, specialist channels (called GLUT4) travel from the centre of the cell to its surface. Once the channel is in place at the surface, glucose can move through, exiting the bloodstream into the cell. In people with Type 2 diabetes, this process doesn’t happen - the cells don’t respond to insulin and they don’t send GLUT4 to the surface. This means that glucose builds up in the bloodstream.

We don’t yet understand how insulin controls the movement of GLUT4, and this is holding back the development of treatments to boost it. Professor Gould has previously found an protein (called Sx4) that plays an important part in moving GLUT4 from the centre of fat cells to the cell surface. He believes that Sx4 could be part of the problem when Type 2 diabetes develops.

Research aims

Professor Gould’s student will grow mouse fat cells in the lab to study the basic biology of how Sx4 does its job of moving GLUT4, and how the cell controls this. Using sophisticated microscopes, the team will also look at exactly where Sx4 does its job inside the fat cells.

Once the team have a greater understanding of how Sx4 works in healthy conditions, they will run experiments to see if, and how, Sx4 behaves differently in Type 2 diabetes. They will perform similar experiments on mouse fat cells that have been changed to be unresponsive to insulin.

Potential benefit to people with diabetes

Understanding more about how insulin keeps our blood glucose levels constant, and how this process goes wrong in people with Type 2 diabetes, will help pave the way for new treatments to help people manage their condition. 

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