The paper by Martin et. al demonstrates the endocrine units success under my leadership in making the pituitary service of international repute. We are now publishing cutting edge studies investigating the increasingly difficult diagnosis of CushingÃ¢ÂÂs disease. In this paper, we have shown that previous suggestions that adding intravenous corticotrophin releasing hormone at the end of the dexamethasone suppression test reduces the specificity of the test, resulting in patients potentially having pituitary surgery that they do not need.
I am also leading research to determine the best options for replacement treatment in pitutiary and adrenal failure.
Another majour area of my research is the control of feeding and metabolism, and this is becoming a very important area of research as the obesity epidemic gets out of control. I now have an Experimental Medicine grant to continue research in this area. I have previously shown the effects of GLP-1 on feeding in rats (Turton etal 1996; Nature) and also that blockade of GLP-1 in rats using exendin (9-39) increases food intake in rats (Meeran etal 1999; Endocrinology). In the Lancet paper in 2003, I have translated this into humans and shown via an experiment of nature that a tumour that secretes GLP-1 has exactly the effect we would predict from our animal studies on humans. The tumour was responsive to ambient glucose levels, and responded by stimulating insulin release which caused delayed hypoglycaemia.
Since then exendin analogues (exanatide) has been licensed to help control blood glucose in patients with diabetes.
Oxyntomodulin is another analogue of glucagon, produced by alternative splicing of the pre-pro glucagon gene. Others in our lab have shown that oxyntomodulin affects food intake in animals and we have now shown that this analogue, when given subcutaneously to humans, can both reduce food intake and increase energy expenditure and hence reduce body weight. This is the subject of my recently acquired Experimental Medicine grant, to investigate the effects of this peptide on metabolism as well as food intake. The next stage is to develop a non toxic non peptide analogue, that can be administered orally.
This is also an area that is attracting a lot of interest amongst juniors and future potential research fellows. As a consequence, metabolic medicine has been awarded the highest number of Academic Clinical Fellows (24 over 5 years) and CLs (10 over 5 years).
I am an author on the nationally accepted guidelines for the management of NETs and a founder member of NETWORK (UK), the national society for the care of patients with carcinoid and other gut hormone tumours. Several of my publications are based on investigations and development of new assays for these tumours.