title: Effects of insulin and glucocorticoids on the leptin system are mediated through free leptin.
abstract: OBJECTIVE
  Insulin and glucocorticoids are known to increase total leptin levels. However, the effects of insulin and glucocorticoids on the components of the leptin system - free leptin (FL), bound leptin (BL) and soluble leptin receptor (SR) - have not been elucidated. The aim of this study was to determine if there is a differential effect of insulin and glucocorticoids on the leptin system.
  
  
  METHODS
  In the first of two studies (study 1), we measured free leptin (FL), bound leptin (BL), a soluble leptin receptor (SR) and insulin, by specific RIA methods, in six healthy subjects on a control day, and subsequently during a hyperinsulinaemic euglycaemic clamp study. In the second study (study 2) we measured the same parameters in six healthy subjects, before (day 1) and during administration of dexamethasone over 3 consecutive days.
  
  
  RESULTS
  In study 1, on the control day FL levels rose over the 16 h monitoring period (P = 0.057) and SR levels declined (P < 0.001), but there was no change of BL levels. Even after accounting for diurnal variation, FL levels increased even more substantially over 12 h of insulin infusion than observed on the control day (P < 0.001). In study 2, mean FL concentration doubled from day 1 to day 2 (P = 0.01) and remained elevated subsequently. In contrast to FL, BL and SR levels remained unchanged during the study. Fasting insulin levels (pmol/l) increased from day 1 to day 2, but this rise only approached significance on day 4 (P = 0.05).
  
  
  CONCLUSIONS
  We conclude that insulin and dexamethasone increase free leptin levels, but do not change the concentrations of bound leptin and soluble leptin receptor. Furthermore, the dexamethasone-induced rise in leptin levels is (at least partially) independent of the effects of glucocorticoid-induced hyperinsulinaemia.
authors.affiliation: The Sir Quinton Hazel Molecular Medicine Research Centre, Department of Biological Sciences, University of Warwick, Coventry, UK.
authors.forename: K
authors.initials: K
authors.lastname: Lewandowski
authors.forename: H S
authors.initials: HS
authors.lastname: Randeva
authors.forename: C J
authors.initials: CJ
authors.lastname: O'Callaghan
authors.forename: R
authors.initials: R
authors.lastname: Horn
authors.forename: G F
authors.initials: GF
authors.lastname: Medley
authors.forename: E W
authors.initials: EW
authors.lastname: Hillhouse
authors.forename: G
authors.initials: G
authors.lastname: Brabant
authors.forename: P
authors.initials: P
authors.lastname: O'Hare
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000097:blood*; D002940:Circadian Rhythm; D003907:Dexamethasone; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood*; D016014:Linear Models; D008297:Male; D011863:Radioimmunoassay / Q000379:methods; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin
chemical_list: D002352:Carrier Proteins; D005938:Glucocorticoids; D007328:Insulin; C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D003907:Dexamethasone