In recent years there has been considerable progress in identifying how insulin signals to the cell's interior. The interaction of insulin with its receptor triggers the formation of phosphatidyl inositol (3, 4, 5) trisphosphate (PIP3) at the plasma membrane which then activates several signal transduction pathways. Perhaps the most important of these is the protein kinase cascade in which 3-phosphoinositide-dependent protein kinase-1 (PDK1) activates protein kinase B (PKB, also called Akt), which then inactivates glycogen synthase kinase 3 (GSK3). PDK1, PKB and GSK3 then phosphorylate many regulatory proteins, thereby mediating many of the actions of insulin. In the lecture, I will present a brief overview of the pathway and the recent genetic evidence that has validated it. I will also discuss the possibility of targeting particular components of the pathway to develop drugs that may overcome the resistance to insulin observed in Type-II diabetes and the progress that is being made in each of these areas.
Acknowledgements. The work of our Unit is supported by the UK Medical Research Council, The Royal Society, AstraZeneca, Boeringer Ingelheim, Glaxo Smith Kline, Merck and Co, Merck KGaA and Pfizer.
22 - 24 Mar 2004
British Endocrine Societies