title: Insulin and GH signaling in human skeletal muscle in vivo following exogenous GH exposure: impact of an oral glucose load.
abstract: BACKGROUND
  GH induces acute insulin resistance in skeletal muscle in vivo, which in rodent models has been attributed to crosstalk between GH and insulin signaling pathways. Our objective was to characterize time course changes in signaling pathways for GH and insulin in human skeletal muscle in vivo following GH exposure in the presence and absence of an oral glucose load.
  
  
  METHODS
  Eight young men were studied in a single-blinded randomized crossover design on 3 occasions: 1) after an intravenous GH bolus 2) after an intravenous GH bolus plus an oral glucose load (OGTT), and 3) after intravenous saline plus OGTT. Muscle biopsies were taken at t = 0, 30, 60, and 120. Blood was sampled at frequent intervals for assessment of GH, insulin, glucose, and free fatty acids (FFA).
  
  
  RESULTS
  GH increased AUC(glucose) after an OGTT (p<0.05) without significant changes in serum insulin levels. GH induced phosphorylation of STAT5 independently of the OGTT. Conversely, the OGTT induced acute phosphorylation of the insulin signaling proteins Akt (ser(473) and thr(308)), and AS160.The combination of OGTT and GH suppressed Akt activation, whereas the downstream expression of AS160 was amplified by GH. WE CONCLUDED THE FOLLOWING: 1) A physiological GH bolus activates STAT5 signaling pathways in skeletal muscle irrespective of ambient glucose and insulin levels 2) Insulin resistance induced by GH occurs without a distinct suppression of insulin signaling proteins 3) The accentuation of the glucose-stimulated activation of AS 160 by GH does however indicate a potential crosstalk between insulin and GH.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00477997.
authors.affiliation: Department of Internal Medicine and Endocrinology (MEA) and Medical Research Laboratories, Aarhus University Hospital, Aarhus, Denmark. tk-h@ki.au.dk
authors.forename: Thomas
authors.initials: T
authors.lastname: Krusenstjerna-Hafstrøm
authors.forename: Michael
authors.initials: M
authors.lastname: Madsen
authors.forename: Mikkel H
authors.initials: MH
authors.lastname: Vendelbo
authors.forename: Steen B
authors.initials: SB
authors.lastname: Pedersen
authors.forename: Jens S
authors.initials: JS
authors.lastname: Christiansen
authors.forename: Niels
authors.initials: N
authors.lastname: Møller
authors.forename: Niels
authors.initials: N
authors.lastname: Jessen
authors.forename: Jens O L
authors.initials: JO
authors.lastname: Jørgensen
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001706:Biopsy; D018592:Cross-Over Studies; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000008:administration & dosage*; D005951:Glucose Tolerance Test; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D016037:Single-Blind Method
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin; D019382:Human Growth Hormone; D005947:Glucose