Not all beta cells are the same!

We've just posted a new paper from graduate student Amanda Schukarucha Gomses online!
(www.biorxiv.org/content/10.1101/2024.12.02.626463v1)!

We all know that people are differ from each other, and likewise that patients with diabetes are also different from one another. Not everyone with type 2 diabetes has it in the same waym, or is equally affected by it. In our group, we study the cells in the pancreas that make insulin and other hormones. These cells, called pancreatic beta cells, are also highly variable or heterogeneous - even the (tens of) thousands of beta cells within an individual are highly variable in how they work. Exactly why one beta cell can differ so much from another remains unclear. In fact the differences themselves have not been fully described. What has become increasingly apparent in recent years is that this heterogeneity in beta-cells is important to how a pancreatic islet works (or doesn't work!).

In the paper we’ve just posted, Amanda from our group explores some of this variability between pancreatic beta cells in health and diabetes. For several years now, Amanda has been studying something called glycine, which is an amino acid that acts as a key signal controlling the activity of pancreatic beta cells. It works by tickling specific proteins on the cell called receptors. These receptors are important because they are linked, genetically, to type 2 diabetes and obesity. Previous work from our group showed that these glycine receptors seem to be decreased in type 2 diabetes.

So Amanda wondered, firstly, whether the reduction in these glycine receptors in type 2 diabetes was because of diabetes itself or a consequence of elevated blood sugar. She was able to show that the glycine receptors are downregulated by hyperglycemia. While doing this, she noticed that the activity of these glycine receptors varies tremendously between beta cells, even cells from the same organ donor. Although in general, the activity of these receptors is down in type 2 diabetes, perhaps more surprising was just how different their activity could be between individual beta cells.

To explore what might be responsible for that variation in receptor activity, Amanda performed patch-seq experiments with other members of our team who have used that technique before. She was able to show the relationship between specific genes within a beta cell and the amount of glycine receptor activity in those cells. So what does this mean? Understanding glycine receptors is important because of the link with diabetes, but studying them is also challenging. Because this receptor doesn’t seem so active in mice or rats, we are pretty limited in how we can study it. In short, we need access to human tissue through our tissue bank to study these cells. The results from this study provide a molecular roadmap to understanding the heterogeneity of beta cells and their activity and how this changes in diabetes, thus contributing to our understanding of human insulin secretion in health and diabetes.