title: Growth hormone (GH)-induced insulin resistance is rapidly reversible: an experimental study in GH-deficient adults.
abstract: BACKGROUND
  It is clinically relevant and of physiological interest to investigate whether GH-induced insulin resistance depends on the timing of GH exposure relative to when insulin sensitivity is assessed.
  
  
  OBJECTIVE
  GH-induced insulin resistance is rapidly reversible.
  
  
  METHODS
  Eight male GH-deficient patients underwent a 6-h euglycemic-hyperinsulinemic glucose clamp thrice in a randomized crossover design receiving either no GH (study 0), a 7-h GH infusion (0.2-0.3 mg in total) that terminated 5 h before the clamp (study 1), or a similar GH infusion timed to continue during the first hour of the clamp (study 2). A muscle biopsy was obtained 30 min into the clamp. The patients were compared with eight healthy untreated control subjects (study c).
  
  
  METHODS
  The glucose infusion rate, indirect calorimetry, and free fatty acid metabolism were assessed. In muscle biopsies, protein phosphorylation of signal transducer and activator of transcription 5, Akt, and Akt substrate 160 (phospho-Akt substrate signal) and gene expression of IGF-I and SOCS1-3 were assessed.
  
  
  RESULTS
  Insulin sensitivity differed significantly between the GH-deficiency studies (P = 0.005) with distinct insulin resistance in study 2 and increased insulin sensitivity in study 0 [area under the glucose infusion rate curve (mg/kg · min): 1663 ± 151 (study 0) vs. 1482 ± 166 (study 1) vs. 1123 ± 136 (study 2) vs. 1492 ± 229 (control group)]. Free fatty acid levels and lipid oxidation were elevated in response to GH exposure but became suppressed during the clamp. IGF-I and SOCS3 gene expression was increased in study 2.
  
  
  CONCLUSIONS
  Very-low-dose GH exposure evokes acute insulin resistance that subsides after 5 h. This time-dependent reversibility should be considered when assessing the impact of GH on glucose homeostasis.
authors: Department of Internal Medicine and Endocrinology and Medical Research Laboratories, Aarhus University Hospital, Denmark. tk-h@dadlnet.dk
authors: T
authors: T
authors: Krusenstjerna-Hafstrøm
authors: B F
authors: BF
authors: Clasen
authors: N
authors: N
authors: Møller
authors: N
authors: N
authors: Jessen
authors: S B
authors: SB
authors: Pedersen
authors: J S
authors: JS
authors: Christiansen
authors: J O L
authors: JO
authors: Jørgensen