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Publication : Enhanced insulin sensitivity in mice lacking ganglioside GM3.

First Author  Yamashita T Year  2003
Journal  Proc Natl Acad Sci U S A Volume  100
Issue  6 Pages  3445-9
PubMed ID  12629211 Mgi Jnum  J:82723
Mgi Id  MGI:2654958 Doi  10.1073/pnas.0635898100
Citation  Yamashita T, et al. (2003) Enhanced insulin sensitivity in mice lacking ganglioside GM3. Proc Natl Acad Sci U S A 100(6):3445-9
abstractText  Gangliosides are sialic acid-containing glycosphingolipids that are present on all mammalian plasma membranes where they participate in recognition and signaling activities. We have established mutant mice that lack GM3 synthase (CMP-NeuAc:lactosylceramide alpha2,3-sialyltransferase; EC 2.4.99.-). These mutant mice were unable to synthesize GM3 ganglioside, a simple and widely distributed glycosphingolipid. The mutant mice were viable and appeared without major abnormalities but showed a heightened sensitivity to insulin. A basis for the increased insulin sensitivity in the mutant mice was found to be enhanced insulin receptor phosphorylation in skeletal muscle. Importantly, the mutant mice were protected from high-fat diet-induced insulin resistance. Our results show that GM3 ganglioside is a negative regulator of insulin signaling, making it a potential therapeutic target in type 2 diabetes.
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