An enzyme known to attach sugar to proteins in cells is revealed to have a role in insulin resistance in mice in Nature. Overexpression of the enzyme in the livers of mice causes insulin resistance and dyslipidaemia, underscoring the pivotal contribution of sugar modifications to insulin resistance and type 2 diabetes.
The study of Ronald Evans and colleagues uncovers that O-GlcNAc transferase (OGT) harbours a new type of lipid-binding site, and that, on insulin stimulation, OGT is recruited to the plasma membrane of the cell by the lipid phosphatidylinositol 3,4,5-trisphosphate. There, OGT specifically decorates proteins from the insulin signalling pathway with sugars, impeding their activity and dampening the insulin response.
The work indicates that nutritional cues may regulate insulin signalling through OGT and suggests that modification of the OGT pathway may be linked to insulin resistance, obesity and type 2 diabetes.
Ronald Evans (The Salk Institute, La Jolla, CA, USA)
(C) Nature press release.
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