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.

• Authors: 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
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 100 Issue 6 Pg. 3445-9 (Mar 18 2003) ISSN: 0027-8424 [Print] United States
• PMID: 12629211 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dietary Fats
• G(M3) Ganglioside
• Sialyltransferases
• haematoside synthetase
• Receptor, Insulin

Topics

• Animals
• Dietary Fats (administration & dosage)
• G(M3) Ganglioside (deficiency)
• Gene Targeting
• Insulin Resistance (physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Phosphorylation
• Receptor, Insulin (metabolism)
• Sialyltransferases (deficiency, genetics)
• Signal Transduction