Enhanced insulin sensitivity in mice lacking ganglioside GM3

Tadashi Yamashita, Akira Hashiramoto, Martin Haluzik, Hiroki Mizukami, Shoshannah Beck, Aaron Norton, Mari Kono, Shuichi Tsuji, Jose Luis Daniotti, Norbert Werth, Roger Sandhoff, Konrad Sandhoff, Richard L. Proia*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

396 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)3445-3449
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number6
DOIs
StatePublished - Mar 18 2003

ASJC Scopus subject areas

  • General

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