title: No difference in glycosphingolipid metabolism and mitochondrial function in glucocorticoid-induced insulin resistance in healthy men.
abstract: OBJECTIVE
  Glucocorticoids (GCs) are well known to induce insulin resistance; however, mechanisms that cause the impairement of the insulin signaling pathway have not yet been identified. In this study we measured whether GC-induced insulin resistance in humans is related to changes in muscle ceramide, GM3, and muscle mitochondrial function.
  
  
  METHODS
  In a randomized, placebo-controlled, double-blind, dose-response intervention study, 32 healthy males (aged 22 ± 3 years; body mass index 22.4 ± 1.7 kg/m(-2)) were allocated to prednisolone (PRED) 7.5 mg once daily (n = 12), PRED 30 mg once daily (n = 12), or placebo (n = 8) for 2 weeks using block randomization. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp before and after treatment. Muscle biopsies were performed to measure ceramide, monosialodihexosylganglioside (GM3), and mitochondrial function.
  
  
  RESULTS
  Peripheral insulin sensitivity was dose dependently decreased after the PRED treatment. Muscle ceramide and GM3 concentration and mitochondrial function were not altered by 2 weeks of PRED treatment.
  
  
  CONCLUSIONS
  Short-term GC treatment dose dependently impaired whole-body insulin sensitivity in healthy males, without concomitant changes in muscle ceramide, GM3, or mitochondrial function. These findings suggest that other mechanisms play a role in GC-related impairment of insulin sensitivity.
authors: Department of Endocrinology and Metabolism, Academic Medical Center, Meibergdreef 9 F5-167, 1105 AZ, Amsterdam, The Netherlands. m.brands@amc.uva.nl
authors: M
authors: M
authors: Brands
authors: D H
authors: DH
authors: van Raalte
authors: M
authors: M
authors: João Ferraz
authors: H P
authors: HP
authors: Sauerwein
authors: A J
authors: AJ
authors: Verhoeven
authors: J M F G
authors: JM
authors: Aerts
authors: M
authors: M
authors: Diamant
authors: M J
authors: MJ
authors: Serlie
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005679:G(M3) Ganglioside / Q000378:metabolism; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D006028:Glycosphingolipids / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism; D010919:Placebos; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002518:Ceramides; D005679:G(M3) Ganglioside; D005938:Glucocorticoids; D006028:Glycosphingolipids; D007328:Insulin; D010919:Placebos; D011239:Prednisolone