Prominent increase in plasma ganglioside GM3 is associated with clinical manifestations of type I Gaucher disease.
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.
Ghauharali-van der Vlugt
Karen
K
Department of Medical Biochemistry and Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
Langeveld
Mirjam
M
Poppema
Aldi
A
Kuiper
Sijmen
S
Hollak
Carla E M
CE
Aerts
Johannes M
JM
Groener
Johanna E M
JE
D016022:Case-Control Studies; D015331:Cohort Studies; D005679:G(M3) Ganglioside / Q000097:blood*; D005776:Gaucher Disease / Q000097:blood / Q000473:pathology*; D006801:Humans
D005679:G(M3) Ganglioside