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A protein that helps prevent diabetes could be a target for future treatments: Q&A with Thilo Speckmann

July 17, 2018
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In Dr. Francis Lynn’s lab, part of the Canucks for Kids Fund Childhood Diabetes Laboratories at BC Children's Hospital, researchers are going deep inside the inner workings of cells to study how diabetes develops on a molecular level. They’re studying a specific type of insulin-producing cell in the pancreas known as pancreatic beta cells. Diabetes occurs when these cells stop producing insulin or when the body stops recognizing and responding to insulin.  

A recent study by Dr. Lynn and his colleagues shows how a particular protein called NPAS4 reduces the likelihood of diabetes developing. This research could one day lead to the development of a new therapy that raises levels of this protein or helps it work more effectively to stop the progression type 2 diabetes, a life-long health condition that is becoming more common in children and young people in Canada.

Thilo Speckmann, a UBC doctoral student supervised by Dr. Lynn, talks to us about how the researchers in the Lynn Lab are working to learn more about beta cells and how and why they’re working to lay the ground work for new therapies and preventative treatments for diabetes.

What was the goal of this study?
In this study, we set out to understand the role a DNA-binding transcription factor called NPAS4 plays in the function of pancreatic beta cells. A DNA-binding transcription factor is a protein involved in the transfer of genetic information. Transcription factors turn genes “on” and “off.” When working properly, transcription factors ensure the right genes are expressed in the right cells at the right times. 

In our study, we show reduced levels of NPAS4 in people with type 2 diabetes, which suggests this protein may help prevent beta cell failure and diabetes. Thus, we set out to confirm this by learning more about what NPAS4 does in the body.

What did you find?
We discovered that NPAS4 plays an important role in beta cells. When blood sugar levels rise, beta cells release insulin, a hormone that helps the body use sugar for energy. We found that when high blood sugar levels activate beta cells to release insulin, NPAS4 also becomes active. NPAS4 helps ensure beta cells generate energy that powers them to produce and release insulin.

We looked at mice that did not have NPAS4 and found their beta cells were less effective at producing energy and releasing insulin. When the body doesn’t produce enough insulin, it can’t break down sugars. As a result, high levels of sugar build up in the blood, leading to diabetes.

Why is this finding important? How might it help children?
This research suggests that if we could find a way to increase levels of NPAS4 or help this protein work more effectively, we might be able to stop the progression of type 2 diabetes or prevent it from developing in the first place. More research will have to be done to determine whether it’s possible to create drugs that improve NPAS4 function and whether these drugs would help people with type 2 diabetes, but this is an important early step.

People used to think of type 2 diabetes as an adult disease – in fact, the condition was sometimes called “adult-onset diabetes.” In the past few decades, however, the number of children and young adults with type 2 diabetes has been increasing. This is likely because of rising obesity rates, as obesity and lack of physical activity in genetically predisposed individuals are major risk factors for type 2 diabetes.

Type 2 diabetes is a serious condition at any age, but it’s particularly devastating in children, who will have to live with the condition for most of their lives. Complications of type 2 diabetes include heart disease, vision problems and limb amputation. By developing new treatments and preventive measures for type 2 diabetes, we can help ensure children who develop this condition are able to grow up healthy.

How did you become interested in this area of research?
I have a close family member who has diabetes, and I wanted to do research that would improve the lives of people of people with this condition.

Joining the Lynn lab was the perfect opportunity to use my background in molecular biology to understand how diabetes develops and how we might be able to create new treatments to stop it.

If there is one thing about this research you’d like to share with the general public what would it be?
I would like to express my gratitude to the Canadian public for supporting health research, which is what made it possible for us to conduct this study in the first place. Scientific research can take a long time and the results aren’t always straightforward, but I’m grateful that Canadians recognize the importance of undertaking this work.

In the Lynn lab, we’re going down to the molecular level to understand how one particular type of protein can prevent a life-changing disease. By studying the inner-workings of the human body at such a basic level, we’re laying the groundwork for a future where we can prevent, treat and cure diabetes. 

This work was supported by the Canucks for Kids Fund Childhood Diabetes Laboratories, the Canadian Institutes of Health Research, the Michael Smith Foundation for Health Research, the Canadian Diabetes Association, and BC Children’s Hospital Foundation.

Dr. Francis Lynn is an investigator at the Canucks for Kids Fund Childhood Diabetes Laboratories at BC Children’s Hospital and an Associate Professor in the Departments of Surgery and Cellular & Physiological Sciences, University of British Columbia.