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Islet transplants and liver regeneration

Project summary

Optimising islet engraftment for long term function in Type 1 diabetes

Dr Shareen Forbes will test a range of approaches to improve the effectiveness of islet transplants. Her work could have a significant and immediate impact on the long-term effectiveness of this treatment and allow more people to benefit from it in the future.

Background to research

Islet transplantation is effective at restoring lost or impaired awareness of hypoglycaemia in people with Type 1 diabetes, but the current process is not perfect. Two donor pancreases are required, sixty per cent of islets are lost during transplantation into the liver and the function of successfully transplanted islets declines over time. Moreover, people with Type 1 diabetes rarely become independent of insulin after an islet transplant and those that do often have to return to insulin therapy later. Research has shown that removing part of the liver promotes liver regeneration and significantly increases the incorporation of transplanted islets into the body of a recipient. It would not be acceptable to purposefully damage the liver of an islet transplant patient, but research by Dr Shareen Forbes has shown that the hormone tri-iodothyronine (T3) and hepatocyte growth factor (HGF) can be used to achieve a similar effect.

Research aims

Using studies of human islet transplant in a mouse model, Dr Forbes will test a range of approaches to increase the incorporation of transplanted islets into the liver. Specifically, she will look at whether human islet incorporation into the mouse liver is increased by adding growth factors or chemicals that promote cell division or by differences in the zone of the liver where the islets are incorporated. T3 and/or HGF will be administered to mice before they are given an islet transplant. A variety of techniques will then be used to see if more islets are taken up by the liver and if their function and longevity depends on being located in a specific region of the liver.

Potential benefit to people with diabetes

By helping to optimise islet transplants, the findings of this research could have a significant and immediate impact on the long-term effectiveness of this treatment and allow more people to benefit from it in the future. Islet transplant patients could potentially receive T3 and/or HGF before undergoing the procedure and a single donor pancreas could potentially be used to restore insulin independence, allowing more effective use of this limited resource.

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