March 08, 2023 Teaching aging cells how to make more insulin

Who:

Dr. Robert Screaton, senior scientist, Sunnybrook Health Sciences Centre, Toronto; associate professor, Department of Biochemistry, University of Toronto

Research highlights/discoveries:

• Discovering how human cells respond to cues to ensure they survive and function properly in the body, with a focus on increasing the release of insulin to delay or prevent the onset of diabetes

Dr. Robert Screaton at a glance:

• Appointed co-chair of the National Research Council, Diabetes Canada (2017)

• Appointed associate professor, Biochemistry Department, University of Toronto (2015)

• Received the Young Scientist Award, Diabetes Canada and the Canadian Institutes of Health Research (CIHR) (2014)

• Earned his Ph.D. in Biochemistry from McGill University (1998)

How did you get interested in diabetes research?

I liked biology as a kid, and my background has been in identifying genes and how they work within the cell. After my Ph.D., I trained at the Salk Institute for Biological Studies in San Diego, California, where we looked at all the genes that help regulate the survival of insulin-producing cells (also called beta cells) that are found in pancreatic islets (groups of cells in your pancreas). What we discovered was a network of genes that talk to each other and, among other things, help metformin work. Metformin is a popular medication used to treat prediabetes and diabetes by lowering blood sugar (glucose)—it has been used for decades but before this, no one could pinpoint exactly how it worked. When I came back to Canada after making that discovery, I became a diabetes researcher focused on how diabetes impairs the normal function of cells and how that may impact future treatment.

What are you working on currently in diabetes?

We are looking at the powerhouse of cells—mitochondria—and how they help break down and convert food into molecules that help insulin-producing cells function properly. We know that as men age, their insulin-producing cells decrease, which can lead to prediabetes and type 2 diabetes. We think that’s due to some sort of dysfunction in the mitochondria. We also found that this decrease happens more rapidly in men than it does in women.

Our previous work showed us that a certain protein in our cells’ mitochondria called ROMO1 is required for mitochondrial health and cell survival. It turns out that if we delete ROMO1 from beta cells in mice, the males—but not the females—get diabetes. We want to figure out how the ROMO1 pathway can be turned back on in men, and also why females don’t need the ROMO1 pathway. Answers to both might lead to new treatments for diabetes.

How would this help in treating prediabetes?

We could try to turn ROMO1 on in males as they age to stimulate the mitochondria to work better, which could offset prediabetes or the progression to type 2 diabetes. The fact that women don’t get diabetes when ROMO1 isn’t there suggests that women have a backup circuit that helps them function normally. If we can identify this pathway and turn it on in men, and turn it up in women, we could delay or prevent the onset of diabetes.

The ultimate goal is to figure out how to maintain or ramp up the activity of insulin-secreting cells to compensate for the effects of aging.

Could this concept be applied to other diseases in the future?

Yes. The problem underlying many human diseases is the loss of normal cell function—whether that’s losing cells, having too many cells, or having cells that stop working properly. It turns out that the machinery that causes cells to grow too much in cancer is the same machinery that prevents cells from regenerating in conditions like type 1 diabetes (T1D) or neurodegeneration (diseases of the central nervous system). We need to know how to turn this machinery off in cancer and back on in T1D or neurodegeneration.

The last word

“Dr. Screaton’s work represents an exciting step forward in understanding how to better help people who are living with prediabetes avoid developing type 2 diabetes,” says Laura Syron, CEO and president of Diabetes Canada. “Preventative breakthroughs like this are critical in tackling the growing epidemic, as six million people are currently living with prediabetes.”

Did you know?

Some long-term diabetes complications, such as heart disease, may begin with prediabetes. That’s why it is important to take a diagnosis of prediabetes seriously and work with your healthcare providers to properly manage your blood sugar. We can all play a role in ending diabetes. Help us fund research like that of Dr. Screaton, which has the power to change lives. Donate today. #LetsEndDiabetes