Research groups

Research

Regulation of glucose uptake by insulin

We are primarily interested in the molecular basis by which insulin stimulates glucose uptake into fat and muscle cells. We know that the activation of protein kinase B (Akt) is central to this effect of insulin, although we have limited clues as to the precise mechanisms involved. Our work centres around:

• Analysis of the regulation and role of two protein kinase B substrates we have recently identified, called PIKfyve and p122RhoGAP, in insulin action.
• Proteomic identification of novel protein kinase B substrates that may play a role in GLUT4 translocation.
• Analysis of insulin signal transduction in insulin resistance in muscle associated with morbid obesity in humans, and how any defects may be reversed by weight loss brought about through surgical interventions.
• Studies on the role of the Rab-family of small GTP binding proteins, and their regulators, in insulin action on glucose uptake.

A broad range of techniques are used in our laboratory including molecular biology, advanced cell biology (including time-lapse confocal microscopy), (phospho)proteomics and high throughput methods for signal transduction analysis.

Insulin-stimulated translocation of GLUT4-GFP in 3T3 L1 adipocytes

Group

Elaine Hill, Matt Wherlock, Sophie Leney, Claire Hudson, Doug Elder, Emma Vincent, Ruby Al-Mokhtar, Bethan Lloyd-Lewis and Jessica Harris.

Recent publications

Hers, I., Wherlock, M., Homma Y, Yagisawa H, and Tavaré, J.M. 2006 Identification of p122RhoGAP (deleted in liver cancer-1) serine-322 as a substrate for protein kinase B and RSK in insulin-stimulated cells. J. Biol. Chem. 281, 4762-4770.

Hers, I., and Tavaré, J.M. 2005 Mechanism of feedback regulation of insulin receptor substrate-1 phosphorylation in primary adipocytes. Biochemical Journal 388 713-720.

Berwick, D.C., Dell, G.C., Welsh, G.I., Heesom, K.J., Hers, I., Fletcher, L.M., Cooke, F.T., and Tavaré, J.M. 2004 Protein kinase B phosphorylation of PIKfyve regulates the trafficking of GLUT4 vesicles.Journal of Cell Science 117 5985-5993.

Berwick, D.C., and Tavaré, J.M. 2004 Identifying protein kinase substrates: hunting for the organ-grinder's monkeys. Trends in Biochemical Sciences 29 227-232.