In type 1 diabetes (T1D), the destruction of insulin-producing beta cells is well known. But another emerging issue— not well understood—is the dysfunction of alpha cells. These cells produce glucagon, a hormone that helps prevent blood sugar from dropping too low. In people with T1D, alpha cells often fail to respond properly when blood sugar gets too low, which can lead to dangerous episodes of hypoglycemia. At the same time, they may release too much glucagon when it’s not needed, contributing to high blood sugar. Despite the critical role of alpha cells in managing blood sugar, we still know very little about how and why they go wrong in T1D.
Emerging research suggests that not all alpha cells are the same—there may be distinct groups with different roles. These unique behaviors may be linked to differences in how the cells are wired or which genes they express. The goal of this project is to understand these differences more clearly and find out how they change in T1D. To do this, I’ll use advanced imaging tools to study living human pancreatic tissue and isolated islets, allowing me to watch alpha cells in action. I’ll also analyze the molecular profiles of these cells to connect what they do with how they’re built.
By uncovering how alpha cell subtypes work—and how they fail in T1D—this research could open the door to better treatments. In the future, restoring proper alpha cell function could help prevent both low and high blood sugar in people with diabetes, improving safety and quality of life.