title: Altered activity of 11beta-hydroxysteroid dehydrogenase types 1 and 2 in skeletal muscle confers metabolic protection in subjects with type 2 diabetes.
abstract: BACKGROUND
  There is little information regarding the regulation of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzymes in skeletal muscle in the setting of type 2 diabetes.
  
  
  OBJECTIVE
  Our objective was to investigate whether there is differential mRNA expression and enzyme activity of 11beta-HSD1 and 11beta-HSD2 in the skeletal muscle of diabetic subjects compared with controls at baseline and in response to dexamethasone.
  
  
  METHODS
  Participants underwent muscle biopsy of vastus lateralis at baseline and after dexamethasone.
  
  
  METHODS
  The study took place at a university teaching hospital.
  
  
  METHODS
  Twelve subjects with type 2 diabetes and 12 age- and sex-matched controls participated.
  
  
  METHODS
  Subjects were given oral dexamethasone, 4 mg/d for 4 d.
  
  
  METHODS
  We assessed 11beta-HSD1, 11beta-HSD2, and H6PDH mRNA levels by quantitative RT-PCR and enzyme activity by percent conversion of [(3)H]cortisone and [(3)H]cortisol, respectively.
  
  
  RESULTS
  At baseline, mRNA levels were similar in diabetic and control subjects for 11beta-HSD1, 11beta-HSD2, and H6PDH. 11beta-HSD1 activity was reduced in diabetic subjects (percent conversion of [(3)H]cortisone to [(3)H]cortisol was 11.4 +/- 2.5% vs. 18.5 +/- 2.2%; P = 0.041), and 11beta-HSD2 enzyme activity was higher in diabetic subjects (percent conversion of [(3)H]cortisone to [(3)H]cortisol was 17.2 +/- 2.6% vs. 9.2 +/- 1.3%; P = 0.012). After dexamethasone, 11beta-HSD1 mRNA increased in both groups (P < 0.001), whereas 11beta-HSD2 mRNA decreased (P = 0.002). 11beta-HSD1 activity increased in diabetic subjects (P = 0.021) but not in controls, whereas 11beta-HSD2 activity did not change in either group. At baseline, there was a significant negative correlation between 11beta-HSD1 and 11beta-HSD2 enzyme activity (r = -0.463; P = 0.026).
  
  
  CONCLUSIONS
  The activities of skeletal muscle 11beta-HSD1 and 11beta-HSD2 are altered in diabetes, which together may reduce intracellular cortisol generation, potentially conferring metabolic protection.
authors.affiliation: Department of Endocrinology and Diabetes, St. Vincent's Hospital, Melbourne, 41 Victoria Parade, Fitzroy 3065, Australia. christina.jang@svhm.org.au
authors.forename: Christina
authors.initials: C
authors.lastname: Jang
authors.forename: Varuni R
authors.initials: VR
authors.lastname: Obeyesekere
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Dilley
authors.forename: Zygmunt
authors.initials: Z
authors.lastname: Krozowski
authors.forename: Warrick J
authors.initials: WJ
authors.lastname: Inder
authors.forename: Frank P
authors.initials: FP
authors.lastname: Alford
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism*; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D003348:Cortisone / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001786:Blood Glucose; D012333:RNA, Messenger; D003907:Dexamethasone; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D003348:Cortisone; D006854:Hydrocortisone