title: 11β-hydroxysteroid dehydrogenase types 1 and 2 activity in subcutaneous adipose tissue in humans: implications in obesity and diabetes.
abstract: BACKGROUND
  The role of 11β-hydroxysteroid dehydrogenase types 1 (11β-HSD-1) and 2 (11β-HSD-2) enzymes in sc adipose tissue is controversial.
  
  
  OBJECTIVE
  The objective of the study was to determine the activity of 11β-HSD-1 and -2 enzymes in the abdominal and leg sc adipose tissue in obesity and diabetes.
  
  
  METHODS
  11β-HSD-1 and -2 enzyme activities in abdominal and leg sc adipose tissue were measured by infusing [2,2,4,6,6,12,12-(2)H7] cortisone (D7 cortisone) and [9,12,12-(2)H3] cortisol (D3 cortisol) via microdialysis catheters placed in sc fat depots.
  
  
  METHODS
  The study was conducted at the Mayo Clinic Clinical Research Unit.
  
  
  METHODS
  Lean nondiabetic (n = 13), overweight/obese nondiabetic (n = 15), and overweight/obese participants with type 2 diabetes mellitus (n = 15) participated in the study.
  
  
  METHODS
  The conversion of infused D7 cortisone to D7 cortisol (via 11β-HSD reductase activity) and D3 cortisol to D3 cortisone (via 11β-HSD dehydrogenase activity) in sc adipose tissue.
  
  
  RESULTS
  Enrichment of D7 cortisone and D3 cortisol were similar in the effluents from both sites in all groups. D3 cortisone enrichment did not differ in the three cohorts, indicating that 11β-HSD-2 enzyme activity (conversion of cortisol to cortisone) occurs equally in all groups. However, D7 cortisol enrichment was detectable in abdominal sc fat of overweight/obese participants with type 2 diabetes mellitus only, implying 11β-HSD-1 reductase activity (conversion of cortisone to cortisol) occurs in obese subjects with type 2 diabetes.
  
  
  CONCLUSIONS
  There is conversion of cortisone to cortisol via the 11β-HSD-1 enzyme pathway in abdominal sc fat depots in overweight/obese participants with type 2 diabetes mellitus. This observation has significant implications for developing tissue-specific 11β-HSD-1 inhibitors in type 2 diabetes mellitus.
authors.affiliation: Endocrine Research Unit (S.D., B.J.N., V.P., A.B., R.B.), Division of Endocrinology, Diabetes, Metabolism, and Nutrition, and Division of Biomedical Statistics and Informatics (R.E.C.), Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: Simmi
authors.initials: S
authors.lastname: Dube
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Norby
authors.forename: Vishwanath
authors.initials: V
authors.lastname: Pattan
authors.forename: Rickey E
authors.initials: RE
authors.lastname: Carter
authors.forename: Ananda
authors.initials: A
authors.lastname: Basu
authors.forename: Rita
authors.initials: R
authors.lastname: Basu
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000201:enzymology*; D050151:Subcutaneous Fat / Q000201:enzymology*
chemical_list: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2