Enhanced insulin sensitivity in mice lacking ganglioside GM3

T Yamashita, A Hashiramoto, M Haluzik… - Proceedings of the …, 2003 - pnas.org
T Yamashita, A Hashiramoto, M Haluzik, H Mizukami, S Beck, A Norton, M Kono, S Tsuji…
Proceedings of the National Academy of Sciences, 2003pnas.org
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 α2, 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 …
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 α2,3-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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