Insulin sensitivity in muscle and adipose: Glucocorticoids, pre-receptorhormone metabolism and tissue specific cross-talk.

Supervisors: Dr Jeremy Tomlinson, Dr Iwona Bujalska and Dr Dave Smith(AstraZeneca)

The epidemic of obesity and type 2 diabetes has focussed attention on theneed to understand the mechanisms that underpin their pathogenesis. Patientswith glucocorticoid (GC) excess develop profound central obesity, insulinresistance and in some cases type 2 diabetes. However, in most patientscirculating GC levels are normal. We have focussed on the tissue specificgeneration of cortisol by the enzyme 11-hydroxysteroid dehydrogenase type 1which is rapidly emerging as a therapeutic target. In addition, we haverecently identified a differential impact of GC upon insulin signaling inhuman adipose tissue and muscle.

The project will use a wide variety of ex vivo and in vitro techniques inhuman adipose tissue biopsies and human and rodent cell lines tocharacterise patterns of gene and protein expression as well as activationof intracellular signalling cascades. The tissue specific impact of GCs uponinsulin action will be explored and manipulated in a variety of systems. Inaddition, using novel cell culture techniques, we will explore theinteraction between human adipose tissue and muscle. As part of thestudentship, some time will also be spent in the research laboratories ofAstraZeneca in Alderley Park.

In summary this is an exciting opportunity for the successful candidate toform part of an already established team investigating the mechanisms ofinsulin resistance with a view to the development of therapeutic strategies.

TO APPLY FOR THE STUDENTSHIP
Please send a full CV (including a statement of research experience andnames of two referees) to Karen Flaye, Division of Medical Sciences, TheMedical School, University of Birmingham, Birmingham, B15 2TT or email:k.flaye@bham.ac.uk

Closing date for applications is Wednesday 21st June 2006.

Informal enquiries should be made to Dr Jeremy Tomlinson via emailJ.W.Tomlinson@bham.ac.uk