The role of islet microRNAs in regulating functional beta cell mass
Dr Bo Liu will study the role of molecules called microRNAs in the growth and survival of insulin-producing beta cells. She aims to find out if beta cell growth can be promoted by manipulating these molecules and/or other factors that the microRNAs interact with. Her work could help to support the development of new therapies for Type 1 and Type 2 diabetes.
Background to research
Insulin-producing beta cells are able to grow in number when faced with metabolic challenges such as pregnancy or obesity, but problems with this process contribute to the development of diabetes in pregnancy (gestational diabetes) and Type 2 diabetes. However, the precise mechanisms involved in these processes have not been identified. In particular, management of depression using drugs in people with diabetes has been associated with reductions in blood glucose levels by a mechanism not yet identified. Dr Bo Liu has been able to show that two key molecules (microRNA-503 and microRNA-33) are less common in mice whose beta cells have increased in number. MicroRNA molecules, which control the expression of particular genes, could therefore be important in cell death, blocking cell division and keeping beta cell numbers constant. Fluoxetine, the active ingredient in the antidepressant Prozac®, is known to increase the number of insulin-producing cells and reduce blood glucose levels in people who have diabetes. The mechanism by which the drug takes effect is not yet known, but may be linked to its ability to reduce microRNA levels.
Dr Bo Liu will study the role of microRNAs in the growth and survival of insulin-producing beta cells and find out if beta cell growth can be promoted by manipulating these molecules and/or their targets. She will use studies in mice to focus on the role of microRNA-503 and microRNA-33 by controlling their activity, studying the impact on beta cell growth and survival and identifying their targets in beta cells. She will also study the actions of the drug fluoxetine and find out if it is able to maintain beta cell function and lower glucose levels by reducing microRNA levels.
Potential benefit to people with diabetes
The work of Dr Liu will provide evidence to inform the development of new therapies to protect insulin-producing beta cells. These could be used prior to islet transplantation, in order to improve the effectiveness of this technique for treating Type 1 diabetes. They might also provide a new treatment to encourage beta cell growth in Type 2 diabetes. Studying the drug fluoxetine could also improve our understanding of its connection with improved blood glucose control in people who have diabetes and depression.