title: Type I Gaucher disease, a glycosphingolipid storage disorder, is associated with insulin resistance.
abstract: BACKGROUND
  Complex glycosphingolipids, in majority the ganglioside GM3, surround the insulin receptor in a special membrane compartment (raft) and modulate signaling through this receptor. Increased levels of GM3 in rafts impair insulin signaling, resulting in insulin resistance. Gaucher disease is a lysosomal storage disorder in which impaired breakdown of glucosylceramide leads to its accumulation in macrophages. Secondary to this defect, GM3 concentrations, for which glucosylceramide is the precursor, in plasma and several cell types are elevated.
  
  
  OBJECTIVE
  We studied the influence of glycosphingolipid storage on whole body glucose and fat metabolism by measuring insulin-mediated (IMGU) and noninsulin-mediated glucose uptake (NIMGU) and suppression of free fatty acids by insulin.
  
  
  METHODS
  We studied six Gaucher patients, either naive to treatment or with considerable remaining burden of disease, and six matched healthy control subjects in the basal state, during an euglycemic and a hyperglycemic clamp with somatostatin measuring NIMGU and during an euglycemic hyperinsulinemic clamp measuring IMGU, using stable isotopes.
  
  
  RESULTS
  NIMGU (both during euglycemia and hyperglycemia) did not differ between patients and control subjects. IMGU was lower in Gaucher patients, compared with controls. Suppression of lipolysis by insulin tended to be less effective in Gaucher patients.
  
  
  CONCLUSIONS
  Gaucher disease, a lysosomal glycosphingolipid storage disorder, is associated with (peripheral) insulin resistance, possibly through the influence of glycosphingolipids on insulin receptor functioning.
authors: Academic Medical Center, Department of Endocrinology and Metabolism (F4-247), Meibergdreef 9, 1105AZ Amsterdam, The Netherlands. m.langeveld@amc.uva.nl
authors: Mirjam
authors: M
authors: Langeveld
authors: Karen J M
authors: KJ
authors: Ghauharali
authors: Hans P
authors: HP
authors: Sauerwein
authors: Mariette T
authors: MT
authors: Ackermans
authors: Johanna E M
authors: JE
authors: Groener
authors: Carla E M
authors: CE
authors: Hollak
authors: Johannes M
authors: JM
authors: Aerts
authors: Mireille J
authors: MJ
authors: Serlie
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D005679:G(M3) Ganglioside / Q000097:blood; D005776:Gaucher Disease / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D005679:G(M3) Ganglioside; D005947:Glucose