title: Impact of growth hormone receptor blockade on substrate metabolism during fasting in healthy subjects.
abstract: BACKGROUND
  Experimental studies in GH-deficient patients and in healthy subjects receiving somatostatin-infusion suggest that GH is an important regulator of substrate metabolism during fasting. These models may not adequately reflect the selective effects of GH, and GH receptor (GHR) blockade offers a new model to define the metabolic role of GH.
  
  
  OBJECTIVE
  The aim of this study was to investigate the impact of GHR blockade on substrate metabolism and insulin sensitivity during fasting.
  
  
  METHODS
  We conducted a randomized, placebo-controlled, crossover study in 10 healthy young men.
  
  
  METHODS
  After 36 h of fasting with saline or pegvisomant (GHR blockade), the subjects were studied during a 4-h basal period and 2.5-h hyperinsulinemic euglycemic clamp.
  
  
  RESULTS
  We measured whole-body and forearm glucose, lipid, and protein metabolism, peripheral insulin sensitivity, and acyl and desacyl ghrelin.
  
  
  RESULTS
  GHR blockade significantly suppressed circulating free fatty acids (1226 +/- 83 vs. 1074 +/- 65 micromol/liter; P = 0.03) and ketone bodies (3080 +/- 271 vs. 2015 +/- 235 micromol/liter; P <or= 0.01), as well as forearm uptake of free fatty acids (0.341 +/- 0.150 vs. 0.004 +/- 0.119 micromol/100 ml x min; P < 0.01) and lipid oxidation (1.3 +/- 0.1 vs. 1.2 +/- 0.1 mg/kg x min; P = 0.03) in the basal period. By contrast, IGF-I levels in either serum or peripheral tissues were not impacted by GHR blockade, and protein metabolism was also unaffected. Basal glucose levels were elevated by GHR blockade, but insulin sensitivity was similar; this was associated with an increased acyl/desacyl ghrelin ratio.
  
  
  CONCLUSIONS
  GHR blockade, without changes in circulating or tissue IGF-I levels, selectively suppresses lipid mobilization and oxidation after short-term fasting. This supports the notion that stimulation of lipolysis is a primary and important effect of GH.
authors.affiliation: Medical Department M, Medical Research Laboratories, Clinical Institute, Aarhus University Hospital, Aarhus Sygehus, DK-8000 Aarhus C, Denmark. louisem@dadlnet.dk
authors.forename: Louise
authors.initials: L
authors.lastname: Moller
authors.forename: Helene
authors.initials: H
authors.lastname: Norrelund
authors.forename: Niels
authors.initials: N
authors.lastname: Jessen
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: Steen B
authors.initials: SB
authors.lastname: Pedersen
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Gaylinn
authors.forename: Jianhua
authors.initials: J
authors.lastname: Liu
authors.forename: Michael O
authors.initials: MO
authors.lastname: Thorner
authors.forename: Niels
authors.initials: N
authors.lastname: Moller
authors.forename: Jens Otto
authors.initials: JO
authors.lastname: Lunde Jorgensen
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D015992:Body Mass Index; D018592:Cross-Over Studies; D005215:Fasting / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015309:Glucose Clamp Technique; D013006:Growth Hormone / Q000172:deficiency*; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008875:Middle Aged; D010649:Phenylalanine / Q000097:blood; D010919:Placebos; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors*; D012016:Reference Values; D016037:Single-Blind Method; D014443:Tyrosine / Q000097:blood; D014508:Urea / Q000378:metabolism; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D010919:Placebos; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D014443:Tyrosine; D010649:Phenylalanine; D007334:Insulin-Like Growth Factor I; D014508:Urea; D013006:Growth Hormone; C406545:pegvisomant