Functional and computational analyses of the regulation of glucagon secretion in health and disease

The level of glucose in the blood is tightly controlled in the body so it can function healthily. The pancreas contains cells that are designed to maintain a constant, healthy level of blood glucose, beta cells and alpha cells. Beta cells secrete insulin, which acts to store away excess glucose when blood glucose levels are too high. In people with diabetes, these cells do not secrete enough insulin and blood glucose levels become dangerously high, known as hyperglycaemia. The alpha cells act when blood glucose becomes too low (hypoglycaemia) by secreting glucagon. This hormone acts to increase blood glucose levels. Diabetes is often characterised by damaged alpha cells; in response to low blood glucose, these cells fail to secrete glucagon. This can be fatal and hypoglycaemia is a major cause of mortality in diabetes. Beta cells have been extensively investigated by scientists but alpha cells have received much less attention.

In this project I will investigate the mechanisms by which glucose controls glucagon secretion from alpha cells and how these mechanisms can go wrong, resulting in the inability of these cells to appropriately secrete glucagon. I will investigate this by measuring electrical activity from alpha cells, as it is their electrical activity that triggers glucagon secretion. I will also study computational models of alpha cell activity.