O-linked beta-N-acetylglucosamine transferase & diabetes

Commentary
Cellscience Reviews Vol 4 No 4
ISSN 1742-8130

Insulin Resistance and the Sugar-Lipid Connection

Marco Falasca

Inositide Signalling Group, Centre for Diabetes and Metabolic Medicine, Institute of Cell and Molecular Science, Barts,
& The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Activation of PI3K (phosphoinositide 3-kinase) is essential for insulin-induced glucose metabolism, such as glucose storage into muscle and fat cells and glycogen synthesis. Activation of PI3K leads to formation of the phosphoinositide PI(3,4,5)P3 that has been demonstrated to be essential for insulin-induced glucose and lipid metabolism. Accumulated PI(3,4,5)P3 activates several serine/threonine kinases containing a PH (pleckstrin homology) domain, including Akt, atypical PKCs, and downstream effectors p70S6 kinase and GSK. A new study by Yang et al. (2008) extends the number of PI(3,4,5)P3-binding proteins in insulin signalling. They identify O-linked beta-N-acetylglucosamine transferase (OGT) as a protein recruited to the plasma membrane through interaction between PI(3,4,5)P3 and a previously unrecognized phosphoinositide-binding domain. Interestingly, OGT induces insulin resistance and dyslipidaemia through a PI(3,4,5)P3-dependent perturbation of insulin signalling. These findings identify a novel cross-talk that may link systemic metabolic status to the regulation of insulin signalling.

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