Endocrine Abstracts

Phosphoinositide 3-kinase (PI3K) signalling pathways are now accepted to be widely important in the mechanisms by which a variety of cell surface receptors can regulate critical cellular functions, such as cell growth, survival and movement. Class I PI3Ks generate the messenger lipids PtdIns(3,4,5)P3 and PtdIns(3,4)P2 in the inner leaflet of the plasma membrane. These two lipids then co-ordinate the regulation of multiple protein targets by binding, with ...

Almost all tumours display increased activity of components of the phosphoinositide 3-kinase (PI3K) signalling pathway. In particular, activating mutations in the PI3K catalytic subunit, p110alpha, and loss of function mutations of the opposing PTEN phosphatase are amongst the most frequent alterations in human cancers. Our current work aims to understand how loss of PTEN function contributes to tumour development through two related projects. Firstly, we are attempting to add...

Type 2 diabetes mellitus (T2DM) is characterized by major disturbances in lipids as well as the defining abnormalities in glucose. In spite of this, our understanding of the control of lipid metabolism is incomplete. In particular, the relative contribution of insulin compared to other regulatory inputs to the determination of liver and total body adiposity is unclear. We have used a loss of function approach to study the requirement for a major downstream target of insulin, t...

The PI3 kinase family plays an important role in controlling many critical biological processes. There is accumulating evidence that PI3 kinase signalling is involving in a range of diseases and that PI3 kinase inhibitors could offer considerable therapeutic potential. This presentation will focus on the discovery and development of PI3 kinase inhibitors for cancer treatment. The availability of potent and selective PI3 kinase inhibitors is particularly timely given the accumu...