title: In vivo activity of 11beta-hydroxysteroid dehydrogenase type 1 and free fatty acid-induced insulin resistance.
abstract: BACKGROUND
  Free fatty acids (FFAs) induce hepatic insulin resistance and enhance hepatic gluconeogenesis. Glucocorticoids (GCs) also stimulate hepatic gluconeogenesis. The aim of this study was to investigate whether the FFA-induced hepatic insulin resistance is mediated by increased activity of hepatic 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), accompanied by elevated hepatic cortisol levels.
  
  
  METHODS
  Following a 10-h overnight fast, six healthy male volunteers were investigated. A euglycaemic hyperinsulinaemic clamp was performed during lipid or saline infusion. To assess hepatic 11beta-HSD1 activity, plasma cortisol levels were measured after oral administration of cortisone acetate during lipid or saline infusion. In addition, 11beta-HSD activities were determined in vivo by calculating the urinary ratios of GC metabolites.
  
  
  RESULTS
  Lipid infusion increased FFAs (5.41 +/- 1.00 vs. 0.48 +/- 0.20 mmol/l; P < 0.005) and significantly increased insulin resistance [glucose infusion rate (GIR) 6.02 +/- 2.60 vs. 4.08 +/- 2.15 mg/kg/min; P < 0.005]. After lipid and saline infusions no changes in 11beta-HSD1 activity were found, neither by changes in cortisone acetate to cortisol conversion nor by differences in urinary free cortisol (UFF) or cortisone (UFE), 5beta-tetrahydrocortisol (THF), 5alpha-THF, cortisone (THE), UFF/UFE and (5alpha-THF + THF)/THE ratios.
  
  
  CONCLUSIONS
  We found no change in hepatic and whole-body 11beta-HSD1 activity during acute FFA-induced insulin resistance. Further studies are necessary to clarify whether 11beta-HSD1 in muscle and adipose tissue is influenced by FFAs and whether 11beta-HSD1 is involved in other conditions of insulin resistance.
authors.affiliation: Department of Endocrinology, Diabetes and Nutrition, Charite Humanmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany. knut.mai@charite.de
authors.forename: K
authors.initials: K
authors.lastname: Mai
authors.forename: V
authors.initials: V
authors.lastname: Kullmann
authors.forename: T
authors.initials: T
authors.lastname: Bobbert
authors.forename: C
authors.initials: C
authors.lastname: Maser-Gluth
authors.forename: M
authors.initials: M
authors.lastname: Möhlig
authors.forename: V
authors.initials: V
authors.lastname: Bähr
authors.forename: A F H
authors.initials: AF
authors.lastname: Pfeiffer
authors.forename: J
authors.initials: J
authors.lastname: Spranger
authors.forename: S
authors.initials: S
authors.lastname: Diederich
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000097:blood / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000652:urine; D000328:Adult; D003348:Cortisone / Q000031:analogs & derivatives / Q000652:urine; D004789:Enzyme Activation; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D007328:Insulin / Q000008:administration & dosage; D007333:Insulin Resistance; D008055:Lipids / Q000008:administration & dosage; D008099:Liver / Q000201:enzymology*; D008297:Male; D011446:Prospective Studies; D013760:Tetrahydrocortisol / Q000652:urine
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008055:Lipids; D013760:Tetrahydrocortisol; D000324:Adrenocorticotropic Hormone; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D005947:Glucose; D003348:Cortisone; D006854:Hydrocortisone