Sex Differences in Islet Stress Responses Support Female β Cell Resilience

This week Science in Vancouver profiled a recent publication in Molecular Metabolism from the labs of Drs. Elizabeth Rideout and James Johnson at UBC, with first author George Brownrigg. This article is an exact replication with minor changes.

Can you provide a brief overview of your lab’s current research focus?

In the Rideout lab we are interested in understanding sex differences in metabolism and metabolic disease. One metabolic disease that shows a clear sex difference in risk between the sexes is type 2 diabetes, a disease caused by the dysfunction of insulin-producing beta cells. Despite a growing body of evidence that there are differences between male and female beta cells, we lack high-quality information on sex differences in this important cell type.

What is the significance of the findings in this publication?

Working with our close collaborators from the Johnson lab at UBC, we used human and rodent samples to compare gene expression and insulin production between male and female beta cells. We made two key findings. In humans, we found that beta cells from female donors showed a greater ability to maintain glucose-stimulated insulin secretion in people living with type 2 diabetes. In mice, we found that female beta cells showed a greater ability to survive and maintain glucose-stimulated insulin secretion during stress. 

Overall, our team showed female islets are able to maintain greater glucose-stimulated insulin secretion across multiple conditions, including during stress and in type 2 diabetes. This detailed information on islet and beta cell stress responses is an important first step toward understanding whether sex differences in beta cells play a role in the male-biased risk of developing type 2 diabetes.

What are the next steps for this research?

Our next step is to identify the stress response pathways that are used by females to maintain more resilient insulin production. To do this, we will inhibit specific stress response pathways during stress, and monitor glucose-stimulated insulin secretion in both males and females. This program of work will tell us which pathways are important in supporting female islet and beta cell function during stress.

If you’d like to mention your funding sources, please list them.

Our research is being funded by Diabetes Canada as part of their recently announced $9M commitment to diabetes research in Canada. It is so critical to support and invest in this kind of research because it has the potential to unlock new insights and breakthroughs in the field of diabetes management, care, and risk-reduction and dramatically improve the lives of those living with diabetes.

Dr. Rideout’s group also received funding from the CIHR Institute of Gender and Health and the Michael Smith Foundation for Health Research. Dr. Johnson’s group is also funded by the CIHR.