We study cellular physiology of pancreatic islets – the small organs that regulate the whole-body sugar levels. Our work will help to find new treatments for diabetes – a disease that is characterised by uncontrolled blood sugar.
Pancreatic islets are micro organs that play a central role in the regulation of whole body sugar (glucose) levels. They are typically composed of three types of endocrine cells: β-cells which secrete glucose lowering insulin; α-cells that produce glucose elevating glucagon and δ-cells which release somatostatin. These cells are able to sense changes of metabolic status and release hormones accordingly. The concerted effort of the three types of cells maintains the blood glucose at an optimal and steady level. Defects in these cells would lead to uncontrolled sugar levels in the body and diabetes.
Islet cells are excitable cells – they are able to generate electrical signals (action potentials) as switches to control the secretion of hormones. Action potentials are formed by opening and closing of ion conductive proteins (ion channels) in the cell membrane and allow rapid changes of intracellular Ca2+ levels. Ca2+ is the primary signal for cell exocytosis – a process in which hormone containing granules to fuse with cell membrane to release their contents into the blood stream. In the Rorsman lab, using human and rodent islets, we are studying the precise mechanisms that control pancreatic hormone secretion. Over years of research, we have developed electrophysiological, optical imaging and biochemical techniques that enabled us to monitor the electrical signals, intracellular Ca2+ and cell exocytosis in the islet cells with great detail and at ultrahigh resolution. With these powerful tools, we aim to address the following questions:
1. How does metabolism regulate glucagon and somatostatin secretion from pancreatic alpha- and delta-cells?
Compared to β-cells, α- and δ-cells are less abundant within the islets, but they also play important roles in maintaining blood glucose at an optimal level. However, the exact mechanisms of how these cells function and respond to circulating factors remain unclear. Using both rodent and human islets, we aim to provide details to understand how these cells operate at a cellular level.
2. How do the islet cells interact?
Islets are composed of β-, α- and δ-cells that are tightly in contact with each other. Not only the hormones they secrete, but also their electrical signals can influence each other. We use histology, electrophysiology and mathematical modelling to study how these cells work together as a unit, a micro-organ.
3. What are the defects of islet hormones secretion in diabetes and how can we develop new treatments?
Together with our collaborators, we have developed various animal models of diabetes. In addition, we also receive islets from donors with type 2 diabetes. With these resources, we are working to understand how the regulation of islet hormones becomes defected in disease. With this information, and together with our clinical colleagues, we aim to carry out clinical trials to test new treatment for diabetes.