Determining the role of arcuate nucleus glucokinase in the regulation of glucose homeostasis

点击翻译按钮获取中文摘要

Diabetes affects 382 million people worldwide including 3.2 million people in the UK alone. Hence most people will know a friend or relative living with this condition. It is the commonest cause of end stage kidney failure and lower limb amputation and diabetics are 10-20 times more likely to go blind than those without diabetes. Management of diabetes costs the National Health Service a staggering 1 million pounds per hour. Sadly no cure has been found and, despite advancements in treatment, diabetes remains a major cause of disability and death. Diabetes is caused by the inability of the body to respond appropriately to high blood glucose (or sugar) levels. Historically, the pancreas, an organ which lies within the abdomen and produces the hormone insulin, was believed to be the main controller of glucose balance. Insulin is a hormone which lowers blood glucose levels. Most treatments to date have been directed at the level of the pancreas. However, there is increasing evidence that certain areas within the brain, particularly an area known as the arcuate nucleus, play a key role. Within the arcuate nucleus there is an increased concentration of glucokinase. Glucokinase is an enzyme which senses and breaks down glucose thereby preventing high glucose levels building up in the bloodstream and therefore preventing the development of diabetes. However, the specific function and mechanism of action of glucokinase within the arcuate nucleus itself is not known. I aim to determine the exact role and function of glucokinase within the arcuate nucleus of rats. Rats have very similar mechanisms of appetite and glucose control to humans and therefore provide excellent models for study. Within my laboratory at Imperial College, I have worked alongside experts in this field to collect pilot data in rat models to determine whether there is any scope in exploring this avenue further. My preliminary work is very promising and shows that increased activity of the glucokinase enzyme within the arcuate nucleus area of the brain improves blood sugar levels and hence should, in theory, protect against the development of diabetes. In understanding this novel pathway within the brain I aim to investigate this area further and establish if there are new undiscovered mechanisms within the brain (rather than pancreas alone) which are involved in blood sugar control and therefore development of diabetes. Once identified, these pathways may provide targets for more optimal treatment of diabetes.