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Publication : Dissociation of the insulin receptor from caveolae during TNFα-induced insulin resistance and its recovery by D-PDMP.

First Author  Sekimoto J Year  2012
Journal  FEBS Lett Volume  586
Issue  2 Pages  191-5
PubMed ID  22200571 Mgi Jnum  J:179985
Mgi Id  MGI:5304963 Doi  10.1016/j.febslet.2011.12.019
Citation  Sekimoto J, et al. (2012) Dissociation of the insulin receptor from caveolae during TNFalpha-induced insulin resistance and its recovery by d-PDMP. FEBS Lett 586(2):191-5
abstractText  Previously, we demonstrated that an inhibitor of ganglioside biosynthesis, d-PDMP, could restore impaired insulin signaling in tumor necrosis factor alpha (TNFalpha)-treated adipocytes by blocking the increase of GM3 ganglioside. Here, we analyzed the interaction between insulin receptor (IR) and GM3 in the plasma membranes using immunoelectron microscopy. In normal adipocytes, most GM3 molecules localized at planar and non-caveolar regions. Approximately 19% of IR molecules were detected in caveolar regions. The relative ratio of IRs associated with caveolae in TNFalpha-treated adipocytes was decreased to one-fifth of that in normal adipocytes, but this decrease was restored by d-PDMP. Thus, we could obtain direct evidence that insulin resistance is a membrane microdomain disorder caused by aberrant expression of ganglioside.
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