Looking for treatments in insulin secretion
Dr Mark Russell is a lecturer at the University of Exeter Medical School. His research interests are focused on diabetes, specifically in the beta cell and understanding the factors that regulate beta cell health.
Dr Russell received a DRWF Pump Priming Grant in 2020.
Dr Russell said: “I was very happy to be awarded one of the Pump Priming awards in 2020.
“My research title for this project is Is mitochondrial STAT3 a novel regulator of insulin secretion? This includes the things that make the beta cell survive and kill the beta cell and insulin secretion from the beta cell.
“Signal transducer and activator of transcription 3 (STAT3) is a type of transcription factor or one of a family of transcription factors that exists within most cell types. These transcription factors are essentially proteins within cells that allow signals from the outside of the cell to be transferred or to be moved and relayed all the way to the nucleus of the cell.”
How is mitochondrial STAT3 different to this?
“Mitochondrial STAT3 is actually very similar to the STAT3 I just described. STAT3 is typically routed to the nucleus. Recent research suggests that STAT3 can be modified at particular locations. Instead of routing it towards the nucleus, route it instead towards the mitochondria. This is because the mitochondria are an important organelle (a small structure in a cell that is surrounded by a membrane and has a specific function) within all cells. They are responsible for the generation of energy in the form of ATP (adenosine triphosphate) in cells. If you cast your mind back to school days, you will probably remember the mitochondria as being called the powerhouse of the cells. This is what they do.”
How might this then be important for beta cells of the pancreas?
“We think this might be particularly important in the pancreas. First of all, this has never been looked at within the pancreas, but the production of ATP from the mitochondria is integrally linked to the secretion of insulin from beta cells. The way in which this works is that glucose from the outside of the cell is taken into the beta cell, and this is metabolised and moved to mitochondria where it is used to generate ATP. This ATP is then used in the process of insulin secretion.”
In your study, how did you modify STAT3 in beta cells to promote its movement to the mitochondria?
“We identified a number of different factors that we could treat beta cells with, which would allow us to increase this modification of STAT3. We also found a number of drugs that we could treat the cells with that were able to block this effect.”
What did you do to assess whether the energy generation and insulin production changes in these cells?
“We needed to understand whether getting STAT3 into the mitochondria would have an affect there at all. To be able to do this, I had to lean quite heavily on my co-investigator on this project, Dr Kate Ellacott, and the very talented Dr Josie Robb, both of whom had a lot of experience in the study of the mitochondria in astrocytes, which are a cell within the brain, and they used this experience and these skills to explore the role of STAT3 in the mitochondria and whether there were changes here, which was an invaluable help.”
How could the results generated from the study help in the design of novel drugs, which could increase insulin production in people with diabetes?
“Our hope is that, once we understand exactly how STAT3 is involved in regulating insulin secretion, then similar sort of drugs can be developed in the same sort of ways.”
What difference did the Pump Priming Award mean to your career as a diabetes researcher?
“I have only been an independent researcher since 2019. This was my first grant as an early career independent researcher, which was a huge shot in the arm to my own confidence to be able to say that some of the ideas that I have are not too bad. This is so important for us, as early career independent researchers, as we need to be able to show that we are fundable. In doing this, it allows us to be more likely to get additional funding.
“Off the back of this, I obtained another grant that funds a related project, which has been really important, particularly at the minute, considering funding has been somewhat constrained following the pandemic.
“I think it is important to thank DRWF for the strong work that they do in the support of diabetes research in the UK. I think it is so important that this sort of research is funded. At the minute, it is really hard to get any sort of funding.
“I am incredibly thankful for DRWF funding this work. Beyond that, it is also important to thank the people who donate and who fundraise for DRWF and, in fact, anyone who does fundraising for any sort of diabetes research. Because without that fundraising, none of this can happen."
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