Dysregulation of glucagon secretion in diabetes: impact of genetics and metabolism
Problems affecting the release of the hormone glucagon are a hallmark of diabetes. A student supervised by Professor Patrick Rorsman will investigate the influence of genetic and physical factors on the mechanisms of glucagon release.
Background to research
Most people with diabetes have heard of insulin, but the condition also involves the overproduction of glucagon, another hormone that has the opposite effect on blood glucose. Insulin is produced when blood glucose levels are high and causes them to fall, whereas glucagon is produced when levels are low, causing them to rise. Glucagon problems contribute to high blood glucose levels, which are a hallmark of diabetes and can lead to serious complications. Diabetes sometimes also results in insufficient production of glucagon when blood glucose levels are low, which makes insulin therapy more difficult and can sometimes result in severe hypos. High blood glucose levels usually inhibit the release of glucagon, but the exact nature of the mechanisms involved is unclear. We do know that glucose prevents the release of glucagon by acting on alpha cells, the cells in the islets of the pancreas that produce it. It is also known that specific types of pore on the cell surface play a key role in this process and that sulphonylurea drugs mimic the effects of glucose by binding to them.
This study aims to establish the role of genetic factors, physical factors (such as age and obesity) and factors related to energy balance in diabetes-related problems with the release of glucagon. A student supervised by Professor Patrick Rorsman will use mouse and human islets and measurements of biochemical, electrical and genetic changes to investigate the mechanisms by which glucagon release is regulated. Glucagon release from human islets will also be compared to factors known to contribute to diabetes (such as age, genetics and body mass index). The student will then attempt to mimic these factors in the lab and correct them using sulphonylureas.
Potential benefit to people with diabetes
This long term goal of this research is to aid the development of new and improved therapies to correct problems that affect the release of insulin and glucagon in diabetes. As sulphonylureas are already used to target these mechanisms, the findings obtained could have a rapid impact on the lives of people with diabetes who use insulin to treat their condition.