Regrowth of Beta Cells with Small Molecule Therapy
Peter Thompson, Ph.D. — University of California San Francisco
Type 1 diabetes (T1D) results when beta cells are destroyed and the body can no longer produce enough insulin to convert the sugar from the foods we eat into energy. A major focus of our work towards a cure for T1D is on identifying the events that occur in the beta cell on the path towards their destruction and the development of diabetes. The process that leads to destruction of beta cells is not well understood, but seems to progress steadily and predictably. In the early stages, generally only small numbers of beta cells are lost but gradually over time, more and more cells are lost. By the time a person becomes diabetic, there are very few beta cells left and therefore not enough insulin. We think that by identifying new events during the progression towards T1D we may be able to design new interventions that could prevent or even reverse the onset of diabetes.
The New Finding
We have recently found that a beta cell growth pathway, called the mTORC1 pathway, gets switched on in a subset of beta cells during the progression towards and the onset of T1D in mice. Intriguingly, the mTORC1 pathway is normally off in the adult beta cell but is switched on under specific conditions and may help beta cells cope with insults that affect their numbers or function. When the mTORC1 pathway is activated in beta cells, it causes them to grow in size, allowing them to make more insulin and it also can promote their progression towards cell division. Therefore,it seems that beta cells may sense that their numbers are starting to decline and attempt to compensate by turning on the mTORC1 pathway.
The Idea And Approach
The aim is to help beta cells grow (increase in size) and divide (increase in number) using small molecules to stimulate the level of mTORC1 activity in the cells that have already switched it on during the onset of T1D. This could increase insulin production by the remaining beta cells and also encourage cell division to generate new beta cells. To this end we will test known small molecules targeting the mTORC1 pathway and screen to identify new mTORC1-stimulating small molecules. We will test the effects of these small molecules of these on beta cell growth and cell division in culture, in diabetic mouse models and human beta cells.
The Expected Outcomes
This approach is completely novel, and will give us exciting insights into how beta cells may be trying to compensate for their declining numbers during the onset of T1D. Importantly, this study will show us whether we can increase the mTORC1 pathway to improve beta cell growth and division as a new therapeutic strategy. Depending on what we find, this could constitute a whole new framework for how to augment the insulin production by existing beta cells and replace lost beta cells in a diabetic person’s body. If we can identify and target the right factors in the mTORC1 pathway, we may be able to reverse the progression towards and onset of diabetes. Ultimately, it would mean that a person with T1D would no longer need insulin injections because they could have sufficient numbers of functioning beta cells to make enough insulin on their own.
I completed my bachelor’s in genetics and master’s in molecular biology, both at the University of Alberta, where I studied birth defects using mouse models. I went on to do a Ph.D. in medical genetics at the University of British Columbia, where I worked on understanding how genes are regulated in stem cells. I am now a post-doctoral scholar at the University of California, San Francisco Diabetes Center.
At a young age I knew I wanted to be a scientist. I was fortunate to have several great mentors along the way through my undergraduate years who gave me opportunities to be involved in research and encouraged me, and that was when I really knew that it was something I wanted to do and could be good at. My graduate school mentors have also had a strong impact in shaping my career.
As a researcher, although my graduate school training was in basic science, I always wanted to use knowledge to make a difference and work on translating that knowledge into better treatments for disease. Type 1 diabetes is among the most common chronic diseases of childhood in the world, and the numbers are on the rise. We still really don’t know why, and the mystery of it really intrigues me. It’s also a very exciting time to be in diabetes research. We have unprecedented technologies that allow us to ask questions that we couldn’t address before, and I really think we’re very close to a cure.
Personally, my family has been affected by diabetes, and as a father of two sons ages 3 and 1, I empathize with parents who are caring for their children who have diabetes.
For me, research is not just a “job”, it is a calling I have been given, and this project is just the beginning. It’s one of the ways I get to play a part in bringing healing to the world. If that resonates with you, and you have a vision to see type 1 diabetes cured, then I invite you to partner with us and together we can work towards that goal.