title: Glucocorticoid Excess Increases Hepatic 11β-HSD-1 Activity in Humans: Implications in Steroid-Induced Diabetes.
abstract: BACKGROUND
  Animal studies indicate that glucocorticoids increase hepatic 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) expression and activity.
  
  
  OBJECTIVE
  Our goal was to determine whether glucocorticoid excess increases cortisol production in the liver via 11β-HSD-1 enzyme pathway in humans.
  
  
  METHODS
  A total of 1 mg each [4-(13)C] cortisone and [9,12,12-(2)H3] cortisol were ingested, and [1,2,6,7-(3)H] cortisol was infused to measure C13 cortisol (derived from ingested [4-(13)C] cortisone) turnover using the triple tracer technique, whereas glucose turnover was measured using isotope dilution technique following [6-6(2)H2] glucose infusion during a saline clamp.
  
  
  METHODS
  This study took place at the Mayo Clinic Clinical Research Unit.
  
  
  METHODS
  Thirty nondiabetic healthy subjects participated.
  
  
  METHODS
  Subjects were randomized to hydrocortisone (n = 15) or placebo 50 mg twice daily (n = 15) for 1 week.
  
  
  METHODS
  Hepatic cortisol production and endogenous glucose production were measured.
  
  
  RESULTS
  Plasma cortisol concentrations were higher throughout the study period in hydrocortisone group. Rates of appearance of C13 cortisol and hepatic C13 cortisol production were higher in hydrocortisone vs placebo group, indicating increased hepatic 11β-HSD-1 activity. Higher plasma cortisol and presumably higher intrahepatic cortisol was associated with impaired suppression of endogenous glucose production in hydrocortisone vs placebo group.
  
  
  CONCLUSIONS
  Chronic glucocorticoid excess increases intrahepatic cortisone to cortisol conversion via the 11β-HSD-1 pathway. The extent to which this causes or exacerbates steroid induced hepatic insulin resistance remains to be determined.
authors: Endocrine Research Unit (S.D., M.Q.S., A.B., R.A.R., R.B.), Division of Endocrinology, Diabetes, Nutrition; Mayo Clinic, Rochester, MN 55905.
authors: Simmi
authors: S
authors: Dube
authors: Endocrine Research Unit (S.D., M.Q.S., A.B., R.A.R., R.B.), Division of Endocrinology, Diabetes, Nutrition; Mayo Clinic, Rochester, MN 55905.
authors: Michael Q
authors: MQ
authors: Slama
authors: Endocrine Research Unit (S.D., M.Q.S., A.B., R.A.R., R.B.), Division of Endocrinology, Diabetes, Nutrition; Mayo Clinic, Rochester, MN 55905.
authors: Ananda
authors: A
authors: Basu
authors: Endocrine Research Unit (S.D., M.Q.S., A.B., R.A.R., R.B.), Division of Endocrinology, Diabetes, Nutrition; Mayo Clinic, Rochester, MN 55905.
authors: Robert A
authors: RA
authors: Rizza
authors: Endocrine Research Unit (S.D., M.Q.S., A.B., R.A.R., R.B.), Division of Endocrinology, Diabetes, Nutrition; Mayo Clinic, Rochester, MN 55905.
authors: Rita
authors: R
authors: Basu
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D005938:Glucocorticoids; D007328:Insulin; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D005947:Glucose; D006854:Hydrocortisone