Enhanced insulin sensitivity in mice lacking ganglioside GM3

YAMASHITA T.; HASHIRAMOTO A.; HALUZIK M.; MIZUKAMI H.; BECK S.; NORTON A.; KONO M.; TSUJI S.; DANIOTTI J.L.; WERTH N.; SANDHOFF R.; SANDHOFF K.; PROIA R.L.

NATL ACAD SCIENCES

Lugar: Washington DC, USA; Año: 2003 vol. 100 p. 3445 - 3445

angliosides 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.