Determine how changes in blood glucose can affect hunger and its role in diabetes

This project aims to determine how changes in blood glucose can affect hunger and the drive to feed and examine how this can be altered in conditions such as diabetes.

Hypoglycaemia (low blood glucose) is a complication of the treatment of diabetes with insulin. It is feared by people with diabetes and is associated with increased risk of death. One of the important defences against a falling blood glucose is the generation of hunger- a potent defence which both warns and directs towards corrective action to help restore blood glucose. A subset of people with diabetes develop defective defensive responses to and warning symptoms (including hunger) of hypoglycaemia. This puts them at a markedly increased risk of suffering severe episodes of hypoglycaemia.

We want to determine how hypoglycaemic feeding is triggered and the mechanisms by which this may become altered in diabetes. To examine this in murine models, we will combine the skills of Evans’ laboratory (hypoglycaemia, insulin clamp methodology, operant conditioning feeding assessment) located within the Institute of Metabolic Science with broader interest and expertise in appetite and feeding with Krashes’ laboratory (neurocircuitry of feeding) to examine how and where glucoprivic feeding maps onto both conventional feeding pathways and also the neurocircuitry which triggers other counter-regulatory responses to hypoglycaemia. The student will examine how this adapts after exposure to antecedent hypoglycaemia. Finally, they will examine potential therapeutic targets to boost/ restore or prevent the loss of protective hunger in diabetes with recurrent hypoglycaemia.