We demonstrated the molecular pathogenesis of type 2 diabetes and insulin resistance focusing on the interaction between insulin receptor and GM3 ganglioside in adipocytes and propose a working hypothesis "metabolic disorders, such as type 2 diabetes, are membrane microdomain disorders caused by aberrant expression of gangliosides". It is expected that the development of novel diagnosis of metabolic syndrome by identifying the specific ganglioside species and a therapeutic strategy "membrane microdomain ortho-signaling therapy".