Editor's Summary

21 February 2008

Insulin resistance

The modification of nuclear and cytoplasmic proteins by O-linked N-acetylglucosamine (O-GlcNAc) is emerging as a key regulator for many cellular processes. One suspected role is as a nutrient sensor, linked to glucose flux through the hexosamine biosynthetic pathway. A study of the role of O-GlcNAc in the response to glucose flux reveals a new type of lipid binding site on the enzyme O-GlcNAc transferase (OGT): on insulin stimulation, the lipid phosphatidylinositol 3,4,5-trisphosphate binds to OGT, recruiting it to the plasma membrane. OGT then decorates insulin signalling pathway proteins with sugars, impeding their activity and dampening the insulin response. Overexpression of OGT in the liver of mice causes insulin resistance and dyslipidaemia. Abnormal O-GlcNAc modification of insulin signalling may therefore contribute to insulin resistance, obesity and type-2 diabetes.

Article: Phosphoinositide signalling links O-GlcNAc transferase to insulin resistance

Xiaoyong Yang, Pat P. Ongusaha, Philip D. Miles, Joyce C. Havstad, Fengxue Zhang, W. Venus So, Jeffrey E. Kudlow, Robert H. Michell, Jerrold M. Olefsky, Seth J. Field & Ronald M. Evans

doi:10.1038/nature06668

Abstract | Full Text | PDF (692K) | Supplementary information