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Enhanced insulin sensitivity in mice lacking ganglioside GM3.


ABSTRACT: 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.

SUBMITTER: Yamashita T 

PROVIDER: S-EPMC152312 | biostudies-literature | 2003 Mar

REPOSITORIES: biostudies-literature

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Enhanced insulin sensitivity in mice lacking ganglioside GM3.

Yamashita Tadashi T   Hashiramoto Akira A   Haluzik Martin M   Mizukami Hiroki H   Beck Shoshannah S   Norton Aaron A   Kono Mari M   Tsuji Shuichi S   Daniotti Jose Luis JL   Werth Norbert N   Sandhoff Roger R   Sandhoff Konrad K   Proia Richard L RL  

Proceedings of the National Academy of Sciences of the United States of America 20030310 6


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 heighte  ...[more]

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