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How do beta cells know how to release insulin?

Project summary

Our cells have engines, called mitochondria, which power them. In insulin-making cells, the mitochondria tell the cells how and when to release insulin. When blood sugar levels are high, for example when someone has type 2 diabetes, this process stops working properly. Dr Aida Martinez-Sanchez wants to investigate why this happens by studying how the gene Mtfp1 plays a part how beta cell mitochondria behave. Understanding this could help researchers to develop better treatments that may stop type 2 diabetes from progressing.

Background to research

Type 2 diabetes can develop when the insulin-producing beta cells in the pancreas stop working properly and don’t release enough insulin.

Mitochondria are structures inside cells that work like tiny engines, releasing energy to help the cells to do their jobs. In beta cells, the mitochondria have another important role, telling the cells when and how to release the right amount of insulin. Having high blood sugar levels over a long period of time can have an impact on how well they’re able to do this, meaning beta cells start to make even less insulin and type 2 diabetes can get worse over time.

Our genes contain instructions on how to make different proteins, which are needed for all sorts of processes to keep us alive and healthy. One particular gene, Mtfp1, makes a protein that controls the shapes of beta cell mitochondria. 

Research aims

Dr Martinez-Sanchez and her PhD student want to understand how Mtfp1 affects mitochondria and, in turn, the way beta cells release insulin when blood sugar levels are high. They’ll do this by taking beta cells from humans and mice with high blood sugar. They’ll use genetic scissors, known as CRISPR technology, to chop out the Mtfp1 gene from the cells’ DNA. Then they’ll check the shape of the beta cells’ mitochondria with a powerful microscope and see how much insulin is released.

They also want to find out if high blood sugar levels reduce the amount of Mtfp1 inside beta cells. They’ll expose beta cells to different amounts of sugar and see what happens to Mtfp1 in the cells. All of this should help Dr Martinez-Sanchez and her PhD student figure out the role of Mtfp1 in why beta cells go wrong in type 2 diabetes.

Potential benefit to people with diabetes

Understanding in more detail how beta cells behave and fail in type 2 diabetes could help researchers to develop new treatments that keep beta cells healthy. It could even stop type 2 diabetes from progressing. 

This project could also help us better understand how existing treatments for type 2 diabetes work and how to improve them, to make sure more people living with the condition have healthy blood sugar levels and a much lower risk of developing diabetes complications. 

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