title: Glucocorticoids fail to cause insulin resistance in human subcutaneous adipose tissue in vivo.
abstract: BACKGROUND
  It is widely believed that glucocorticoids cause insulin resistance in all tissues. We have previously demonstrated that glucocorticoids cause insulin sensitization in human adipose tissue in vitro and induce insulin resistance in skeletal muscle.
  
  
  OBJECTIVE
  Our aim was to determine whether glucocorticoids have tissue-specific effects on insulin sensitivity in vivo.
  
  
  METHODS
  Fifteen healthy volunteers were recruited into a double-blind, randomized, placebo-controlled, crossover study, receiving both an overnight hydrocortisone and saline infusion. The tissue-specific actions of insulin were determined using paired 2-step hyperinsulinemic euglycemic clamps incorporating stable isotopes with concomitant adipose tissue microdialysis.
  
  
  METHODS
  The study was performed in the Wellcome Trust Clinical Research Facility, Queen Elizabeth Hospital, Birmingham, United Kingdom.
  
  
  METHODS
  The sensitivity of sc adipose tissue to insulin action was measured.
  
  
  RESULTS
  Hydrocortisone induced systemic insulin resistance but failed to cause sc adipose tissue insulin resistance as measured by suppression of adipose tissue lipolysis and enhanced insulin-stimulated pyruvate generation. In primary cultures of human hepatocytes, glucocorticoids increased insulin-stimulated p-ser473akt/protein kinase B. Similarly, glucocorticoids enhanced insulin-stimulated p-ser473akt/protein kinase B and increased Insulin receptor substrate 2 mRNA expression in sc, but not omental, intact human adipocytes, suggesting a depot-specificity of action.
  
  
  CONCLUSIONS
  This study represents the first description of sc adipose insulin sensitization by glucocorticoids in vivo and demonstrates tissue-specific actions of glucocorticoids to modify insulin action. It defines an important advance in our understanding of the actions of both endogenous and exogenous glucocorticoids and may have implications for the development and targeting of future glucocorticoid therapies.
authors: Centre for Endocrinology, Diabetes, and Metabolism, School of Clinical and Experimental Medicine, Institute of Biomedical Research, University of Birmingham, Queen Elizabeth Hospital, Birmingham, United Kingdom.
authors: Jonathan M
authors: JM
authors: Hazlehurst
authors: Laura L
authors: LL
authors: Gathercole
authors: Maryam
authors: M
authors: Nasiri
authors: Matthew J
authors: MJ
authors: Armstrong
authors: Sarah
authors: S
authors: Borrows
authors: Jinglei
authors: J
authors: Yu
authors: Anton J M
authors: AJ
authors: Wagenmakers
authors: Paul M
authors: PM
authors: Stewart
authors: Jeremy W
authors: JW
authors: Tomlinson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000494:pharmacology; D007260:Infusion Pumps; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010919:Placebos; D050151:Subcutaneous Fat / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D007328:Insulin; D010919:Placebos; D006854:Hydrocortisone