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Giving burned-out beta cells a break

Project summary

Beta cells have the job of making insulin, but when they’re overworked in people living with type 2 diabetes, they start to burn out. Professor Nigel Irwin is exploring a new treatment that hopes to help beta cells recharge, so they carry on making enough insulin to keep blood sugar levels on an even keel.

Background to research

In type 2 diabetes, the insulin you make isn’t used properly, or the pancreas doesn’t make enough insulin. This means insulin-making beta cells in the pancreas must work harder than usual to try to bring down blood sugar levels. Over time they get so tired from all this extra work that they start to shut down, and blood sugar levels rise.

Professor Nigel Irwin and his team have found that giving burned-out beta cells a break from work can help them to relax and come back refreshed, and able to produce more insulin. They’ve discovered a molecule made in the pancreas, called Pancreatic Polypeptide (PP), that instructs beta cells to rest. Now, they want to see if PP could help to give beta cells a better work-life balance and make them better at their job.

Research aims

Professor Irwin will investigate how to harness PP to develop a new treatment to allow beta cells to rest and work more efficiently.

To find out how PP works on beta cells, Professor Irwin and his team will treat mice with type 2 diabetes with PP. They’ll measure how mice who had the treatment respond to a sugary drink, a set meal, and insulin compared to mice who didn’t have the treatment. They’ll also look at samples of beta cells from the mice under microscopes, as well as using techniques in the lab to measure the makeup of the cells, to see if PP treatment changes anything.

The team will also investigate the effects of adding an existing type 2 diabetes drug, called liraglutide. This works like an alarm clock to wake up beta cells to start their workday. They’ll treat mice with liraglutide in the morning and PP at night.

They’ll run tests to find if this combination of treatments will be more beneficial by directing beta cells to work during the day - when they’re most needed to deal with changes in blood sugar levels after meals. While stopping beta cells from working night shifts, and encouraging them to use this time to rest.

Potential benefit to people with diabetes

Over time, type 2 diabetes can get progressively worse as more and more beta cells become exhausted, making blood sugar levels more challenging to manage. This research could discover how to help beta cells avoid burn out and pave the way for innovative new treatments that help people with type 2 diabetes to produce more of their own insulin and slow the condition’s progression.

New treatments would give people steadier blood sugar levels and help them to avoid serious diabetes complications down the line.

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