April 18, 2024 Strengthening cells to prevent and treat diabetes

Who:

Dr. Dan Luciani, investigator with BC Children's Hospital and associate professor at the Department of Surgery, Faculty of Medicine, University of British Columbia

Research highlights/discoveries:

• Building our understanding of the mechanisms of beta cell adaptation and why they fail.

Dr. Dan Luciani at a glance:

• Diabetes Canada, End Diabetes Award Winner (2022)

• Juvenile Diabetes Research Foundation (JDRF) Career Development Award (2013-2018

• Michael Smith Foundation for Health Research (MSFHR) Postdoctoral Fellowship (2008-2009)

• Canadian Diabetes Association (CDA) Postdoctoral Fellowship (2008-2009

How did you get involved in diabetes research?

I started my career as an engineer. I worked in Denmark at the Technical University as a master student and then as a PhD student. Part of what I worked on was biological rhythms and the beta cell is a very nice example of these.

I quickly became very fascinated with the biology and the pathobiology of beta cells. Rather than modelling them on a computer, I began using microscopy, which is a technique that I really love and I use in most of my research. Seeing the cells under the microscope fuelled my desire to understand not just how they function, but how they become dysfunctional.

What have you discovered about beta cells and diabetes?

For people at risk of developing diabetes, their beta cells cannot produce enough insulin, which puts the beta cells under stress. The beta cells try to adapt, but if this fails, a vicious cycle begins—more stress, even less insulin production, higher blood sugars, and eventually a diabetes diagnosis.

Stressed cells activate an internal process called autophagy, which breaks down and recycles the damaged parts of the cell. It appears that the beta cells of people who develop diabetes are having trouble managing their “housekeeping” tasks, or clearing out waste and debris from inside the cell walls.

And that’s one of the big outstanding questions. We don't know why, when and how this mechanism fails.

How is your current research answering this question?

We found evidence that certain proteins in charge of this clean-up process might become dysregulated in stressed beta cells during the development of diabetes. Just like if we don’t take the garbage out at home, excess waste becomes toxic to the cell if it doesn’t get removed.

With the help of Diabetes Canada, we’re testing two proteins that might restore this process and prevent beta cell destruction. These protein treatments could help beta cells “take out their trash” and function properly once again.

What do you hope this research will accomplish?

Our study will show if these proteins can be used to protect beta cells. If they can, we can explore them as a potential way to prevent and treat diabetes.

Beta cells are the only source we have in our bodies for insulin. The loss or failure of beta cells is the crux of what drives diabetes. Understanding their basic cell mechanisms is one of our best shots at preventing this condition.

If we can uncover the specific ways beta cells break down, we can strengthen them to stop diabetes from ever developing.

Why are biological sex differences important in this study?

In our study we’ve decided to take a deeper look at whether or not there are differences based on biological sex.

I think that it is critical to include this, because we’ve known for a long time that there are differences in diabetes incidence between males and females. What's less known is whether or not some of these mechanisms might differ at the cellular level.

What makes Canada a diabetes research destination?

After I first came to Canada in 2005, I was fortunate to be supported by a fellowship from Diabetes Canada, and later my first research grant. The funding I received was a major player in my ability to establish my lab, get my research off the ground, and reach the point where we are now.

And it’s important for people to know that Canada is home to an incredibly strong diabetes research community. The discoveries made in Canada are at the absolute forefront of science. We’ve built up a powerful momentum over many, many years, pushing the world’s knowledge of diabetes exponentially forward.

The last word

“Dr. Luciani’s research will further the scientific understanding of beta cells and the precise mechanisms that lead to the development of diabetes,” says Laura Syron, president and CEO of Diabetes Canada. “For Diabetes Canada, it’s important to invest in fundamental like this to illuminate the causes of diabetes and pursue a promising avenue towards its prevention.”

Did you know?

Understanding beta cells is a critical factor in understanding diabetes, and every new discovery moves our investigators forward. Help us fund research like that of Dr. Luciani which could one day prevent diabetes. Donate now. #LetsEndDiabetes