Specific areas of interest

The Gut's Brain: Enteroendocrine cells and nutrient sensing (Under construction!)

Enteroendocrine (EE) cells are a diffuse network of cells, distributed throughout the intestinal tract that constitute about 1% of epithelial cell population and in total represent the largest endocrine organ in the body. Enteroendocrine cell function to sense and integrate dietary and pathological signals, and in response to these diverse inputs co-ordinate gut function and relay signals to higher centres via hormonal and neural signals. Enteroendocrine cells secrete multiple peptide hormones to orchestrate and co-ordinate food digestion, appetite regulation, gastrointestinal motility, the function of the endocrine pancreas and central nutrient sensing.

Enteroendocrine cells are pivotal in the guts response to nutrients and pathogens and understandably are implicated in the aetiology of serious diseases including obesity and diabetes mellitus.

I cells are a subset of duodenal EEC cells that express the anti-orexigenic and principal satiety peptide hormone cholecystokinin (CCK). CCK is released by I cells in response to luminal nutrients, in particular fatty acids and amino acids. CCK co-ordinates digestion by inhibiting gastric emptying, and by stimulating gallbladder contraction and pancreatic enzyme secretion. I cells are therefore pivotal in the intestinal response to nutrients in so far as they are suggested to sense luminal gut nutrients by membrane bound G protein coupled receptors (GPCRs), integrate nutrient signals and transmit these signals both centrally and peripherally by hormone release, and to the brain by vagal afferent-mediated signalling.

Figure 1. Cross section of mouse duodenum showing

genetically tagged CCK cells (green) stained with anti-cholecystokinin serum

Figure 2. I cells contain CCK and other gut hormones including

ghrelin, GIP and PYY. Immunofluorescent double staining of CCK

containing I cell showing CCK (green) and

ghrelin (red).

The aim of our research is to understand the functions of EE cells in health and disease. In particular to determine:

The role of EE cells in nutrient sensing and feeding behaviour

The involvement of EE cells in the aetiology of serious disease including diabetes mellitus, obesity and idiopathic gut disorders including irritable bowel disease.

To evaluate the value of EE cells as therapeutic targets for treatment of serious disease.

First and foremost I am a physiologist and aim to teach physiology in the 21st century...I think some folk would call this Systems biology, but I prefer to use the P word.