Enhanced insulin sensitivity in mice lacking ganglioside GM3 | Zendy

Tadashi Yamashita | Zendy; Akira Hashiramoto | Zendy; Martin Haluzı́k | Zendy; Hiroki Mizukami | Zendy; Shoshannah Beck | Zendy; Aaron M. Norton | Zendy; Mari Kono | Zendy; Shuichi Tsuji | Zendy; José L. Daniotti | Zendy; Norbert Werth | Zendy; Roger Sandhoff | Zendy; Konrad Sandhoff | Zendy; Richard L. Proia | Zendy

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Enhanced insulin sensitivity in mice lacking ganglioside GM3

Author(s) -

Tadashi Yamashita,

Akira Hashiramoto,

Martin Haluzı́k,

Hiroki Mizukami,

Shoshannah Beck,

Aaron M. Norton,

Mari Kono,

Shuichi Tsuji,

José L. Daniotti,

Norbert Werth,

Roger Sandhoff,

Konrad Sandhoff,

Richard L. Proia

Publication year - 2003

Publication title -

proceedings of the national academy of sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.011

H-Index - 771

eISSN - 1091-6490

pISSN - 0027-8424

DOI - 10.1073/pnas.0635898100

Subject(s) - lactosylceramide , insulin receptor , glycosphingolipid , mutant , ganglioside , sialyltransferase , sialic acid , insulin , biology , regulator , insulin resistance , biochemistry , sphingolipid , insulin receptor substrate , endocrinology , medicine , enzyme , gene

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.

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