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Mechanisms behind GLUT4 movement

Project summary

Investigation into the role of phosphatidyl-inositol-4-phosphate patches and Efr3 in insulin-dependent dispersal of GLUT4 clusters in the plasma membrane of adipocytes

Insulin triggers the movement and dispersal of GLUT4 transporter molecules across the surface of cells, where they help move glucose inside. Professor Bryant’s student will investigate the molecular mechanisms involved in this process to improve our understanding and help identify new targets for Type 2 diabetes treatments.

Background to research

In people without diabetes, blood glucose levels are maintained within a constant range by the action of insulin on fat and muscle tissue after a meal. Insulin works to increase the uptake of glucose by triggering the movement of glucose transporters from storage sites within fat and muscle cells to the cell surface, enabling them to transport glucose inside. This process malfunctions in people with insulin resistance – a key characteristic of Type 2 diabetes. Scientists have recently discovered that insulin not only brings glucose transporters to the cell surface, it also causes them to spread out evenly across the cell surface once there. However, the exact molecular mechanisms involved are not fully understood. Detailed knowledge of this process, and of the other actions of insulin, is vital for the design of new therapies to combat Type 2 diabetes.

Research aims

Professor Nia Bryant will build on previous studies performed in her lab to investigate the mechanisms by which insulin brings about the even distribution of glucose transporter molecules across the surface of cells. Her student will use state-of-the-art techniques to find out how patches enriched with a key molecule on the surface of fat cells are controlled by insulin and contribute to the movement and function of glucose transporters. They will also manipulate molecules thought to play a role in this process and observe the effects.

Potential benefit to people with diabetes

This will be the first study to identify the molecular mechanisms involved in the distribution of glucose transporters on the surface of cells in response to insulin. A better understanding of these mechanisms could aid the design of new therapies to benefit people with Type 2 diabetes.

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