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. |