g(m3)-ganglioside and Metabolic-Syndrome

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".

Topics: Amino Acid Sequence; Biomarkers; Diabetes Mellitus; G(M3) Ganglioside; Humans; Insulin Resistance; Metabolic Syndrome; Molecular Sequence Data

A new concept "Life style-related diseases, such as type 2 diabetes, are a membrane microdomain disorder caused by aberrant expression of gangliosides" has arisen. By examining this working hypothesis, we demonstrate the molecular pathogenesis of type 2 diabetes and insulin resistance focusing on the interaction between insulin receptor and gangliosides in microdomains microdomains and propose the new therapeutic strategy "membrane microdomain ortho-signaling therapy".

Topics: Animals; Biomarkers; Caveolae; Diabetes Mellitus; Diabetes Mellitus, Type 2; G(M3) Ganglioside; Gangliosides; Humans; Hypoglycemic Agents; Insulin Resistance; Metabolic Syndrome; Signal Transduction

Serum GM3 molecular species were quantified in 125 Japanese residents using tandem mass spectrometry multiple reaction monitoring. Individuals were categorized by the presence or absence of metabolic disease risk factors including visceral fat accumulation, hyperglycemia and dyslipidemia. A total of 23 GM3 molecular species were measured, of these, eight were found to be significantly elevated in individuals with visceral fat accumulation and metabolic disease, defined as the presence of hyperglycemia and dyslipidemia. All of the GM3 molecular species were composed of the sphingoid base sphingosine (d18:1 (Δ4)) and, interestingly, six of the eight elevated GM3 molecular species contained a hydroxylated ceramide moiety. The hydroxylated GM3 species were, in order of decreasing abundance, d18:1-h24:0 ≈ d18:1-h24:1 > d18:1-h22:0 » d18:1-h20:0 > d18:1-h21:0 > d18:1-h18:1. Univariate and multiple linear regression analyses were conducted using a number of clinical health variables associated with obesity, type 2 diabetes, metabolic disease, atherosclerosis and hypertension. GM3(d18:1-h24:1) was identified as the best candidate for metabolic screening, proving to be significantly correlated with intima-media thickness, used for the detection of atherosclerotic disease in humans, and a number of metabolic disease risk factors including autotaxin, LDL-c and homeostatic model assessment insulin resistance (HOMA-IR).

Topics: Female; G(M3) Ganglioside; Humans; Male; Metabolic Syndrome; Middle Aged; Risk Factors