Non-Clinical Fellowship

Institution:

Imperial College London

Recipient:

Dr Gavin Bewick

Project:

Investigation of glucose sensing in the brain.

Summary:

The complications of diabetes are the result of poor glycaemic control, which can be prevented by intensive insulin therapy. However, this therapy is limited by hypoglycaemia and the subsequent loss of normal counter regulatory responses. Indeed hypoglycaemia is reported to account for 18% of deaths for type I diabetic subjects. A region of the brain called the hypothalamus is the key site controlling the counter regulatory response to hypoglycaemia.
Glucokinase is the body’s glucose sensor and is expressed at high levels in specialised glucose sensing neurones in the hypothalamus. Their activity is modulated by alterations in glucose concentrations and controls the counter regulatory response to hypoglycaemia.
I hypothesize that alterations in glucokinase function in glucose sensing neurones underlie the development of a defective counter regulatory response to hypoglycaemic in diabetics. To establish the role of glucokinase in the counter regulatory response I will both increase and decrease glucokinase function in the hypothalamus using the gene therapy vector adeno-associated virus. The effect of altered glucokinase function on glucose homeostasis and the counter regulatory response to hypoglycemia will be determined in the non diabetic state and in a model of Type 1 diabetes. This work will establish the neurones critical to the prevention of hypoglycaemia which limits fully successful insulin therapy and results in significant additional morbidity for insulin deficient diabetic subjects and is the first stage to identifying ways to improve the response to hypoglycaemia.

Amount:

£164,189.32