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Untangling how high blood sugars damage beta cells in type 2 diabetes

Project summary

Insulin-making beta cells have recycling centres, called lysosomes, which help to break down waste inside our cells. When someone has type 2 diabetes, this process stops working properly. Dr Aida Martinez-Sanchez wants to investigate why this happens by studying the role a protein called M6PR, plays in controlling how lysosomes in beta cells behave. Understanding this could help researchers to develop better treatments for type 2 diabetes and improve those already available. 

Background to research

As type 2 diabetes progresses insulin-producing beta cells in the pancreas stop working properly and don’t release enough insulin. 

Lysosomes are small but mighty sacs inside our cells that act as the cells’ recycling centres. They contain specific proteins that digest and recycle waste inside the cells, to keep cells working properly. For reasons, we don’t understand yet, high blood sugars over a long period of time can impact how well lysosomes work. 

One specific protein, called M6PR, appears to play a key role in how lysosomes work. But we don’t yet understand its specific role in beta cells or if it contributes to speeding up beta cell failure in type 2 diabetes. 

Research aims

Dr Martinez-Sanchez wants to figure out the role of M6PR in why beta cells go wrong in type 2 diabetes.  

With her team, she’ll use genetic scissors, known as CRISPR technology, to chop out the gene for the M6PR protein from the DNA of mice and donor human beta cells.  

They will use start-of-the-art approaches, including powerful microscopes to find out if their beta cells produce less insulin and contain lysosomes that no longer working correctly.  

They also want to shed light on how drugs used to treat type 2 diabetes, such as GLP-1s work. They’ll expose beta cells with and without the M6PR protein to these different drugs to see what happens to the levels of M6PR in the cells.  

This will help provide a better understanding of what allows beta cells to release the right amount of insulin in response to glucose and how high blood sugar levels stop them from working properly. 

Potential benefit to people with diabetes

Understanding more about how to preserve, restore and enhance beta cell function holds great promise for developing new improved treatments for type 2 diabetes that keep beta cells healthy. 

This research 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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