title: Prominent increase in plasma ganglioside GM3 is associated with clinical manifestations of type I Gaucher disease.
abstract: BACKGROUND
  Patients with Gaucher disease show signs of insulin resistance. The ganglioside GM3 has recently shown to be a negative regulator of insulin sensitivity. In fibroblasts of Gaucher patients, deficient in degradation of glucosylceramide, an increased anabolism of this lipid to gangliosides occurs. The goal of the current study was to establish whether GM3 is elevated in plasma of type I Gaucher disease patients, and is related to disease manifestations.
  
  
  METHODS
  Plasma GM3, glucosylceramide, and ceramide were determined and compared to overall severity of disease, hepatomegaly, and plasma chitotriosidase activity.
  
  
  RESULTS
  The ceramide concentration in plasma of untreated Gaucher patients was slightly but not significantly lower than in controls (median: 9.8 micromol/L, range: 5.7-14.7 micromol/L, (n=40) vs. median: 11.0 micromol/L, range: 5.1-18.0 micromol/L, (n=30)). Glucosylceramide was significantly (p<0.0001) elevated. GM3 was also significantly (p<0.0001) increased (median: 10.2 micromol/L, range: 4.3-19.1 micromol/L, (n=40) vs. median: 3.6 micromol/L, range: 2.7-5.4 micromol/L, (n=30)). Plasma GM3 concentrations correlated with those of plasma chitotriosidase activity (rho=0.45, p=0.0036), overall severity of disease (rho=0.39, p=0.012), and hepatomegaly (rho=0.49, p=0.0015).
  
  
  CONCLUSIONS
  GM3 is strikingly elevated in plasma of most Gaucher patients. The increase is comparable to that of glucosylceramide, the primary storage lipid. The marked elevations in GM3 may play a role in the insulin resistance of Gaucher patients.
authors.affiliation: Department of Medical Biochemistry and Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Karen
authors.initials: K
authors.lastname: Ghauharali-van der Vlugt
authors.forename: Mirjam
authors.initials: M
authors.lastname: Langeveld
authors.forename: Aldi
authors.initials: A
authors.lastname: Poppema
authors.forename: Sijmen
authors.initials: S
authors.lastname: Kuiper
authors.forename: Carla E M
authors.initials: CE
authors.lastname: Hollak
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Aerts
authors.forename: Johanna E M
authors.initials: JE
authors.lastname: Groener
mesh_terms: D016022:Case-Control Studies; D015331:Cohort Studies; D005679:G(M3) Ganglioside / Q000097:blood*; D005776:Gaucher Disease / Q000097:blood / Q000473:pathology*; D006801:Humans
chemical_list: D005679:G(M3) Ganglioside