title: The pattern of growth hormone delivery to peripheral tissues determines insulin-like growth factor-1 and lipolytic responses in obese subjects.
abstract: BACKGROUND
  It is unclear whether the pattern of GH delivery to peripheral tissues has important effects.
  
  
  OBJECTIVE
  The aim of the study was to compare the effects of pulsatile vs. continuous administration of GH upon metabolic and IGF-I parameters in obese subjects.
  
  
  METHODS
  The study was conducted at the General Clinical Research Center at the University of Michigan Medical Center.
  
  
  METHODS
  Four men and five women with abdominal obesity (body mass index, 33 +/- 3 kg/m(2); body fat, 40 +/- 3%) participated in the study.
  
  
  METHODS
  GH (0.5 mg/m(2) . d) was given iv for 3 d as: 1) continuous infusion (C); and 2) pulsatile boluses (P) (15% of the dose at 0700, 1300, and 1800 h and 55% at 2400 h). These trials were preceded by a basal period (B) when subjects received normal saline.
  
  
  METHODS
  Rate of lipolysis and hepatic glucose production were evaluated using stable isotope tracer techniques. The composite index of insulin sensitivity (Matsuda index) was assessed using oral glucose tolerance test.
  
  
  RESULTS
  The increase in plasma IGF-I concentrations was greater (P < 0.05) with continuous GH infusion (211 +/- 31, 423 +/- 38, and 309 +/- 34 microg/liter for B, C, and P, respectively). Muscle IGF-I mRNA was significantly increased (P < 0.05) only after the continuous GH infusion (1.2 +/- 0.4, 4.4 +/- 1.3, and 2.3 +/- 0.6 arbitrary units, for B, C, and P, respectively). Only pulsatile GH augmented the rate of lipolysis (4.1 +/- 0.3, 4.8 +/- 0.7, and 7.1 +/- 1.1 mumol/kg . min for B, C, and P, respectively). GH had no effect on hepatic glucose production, but both modes of GH administration were equally effective in impairing insulin sensitivity.
  
  
  CONCLUSIONS
  These findings indicate that, in obese subjects, discrete components of GH secretory pattern may differentially affect IGF-I generation and lipolytic responses.
authors.affiliation: Division of Metabolism, Endocrinology and Diabetes, University of Michigan, 3920 Taubman Center, Ann Arbor, MI 48109-5354, USA.
authors.forename: Sowmya
authors.initials: S
authors.lastname: Surya
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Horowitz
authors.forename: Naila
authors.initials: N
authors.lastname: Goldenberg
authors.forename: Alla
authors.initials: A
authors.lastname: Sakharova
authors.forename: Matthew
authors.initials: M
authors.lastname: Harber
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Cornford
authors.forename: Kathy
authors.initials: K
authors.lastname: Symons
authors.forename: Ariel L
authors.initials: AL
authors.lastname: Barkan
mesh_terms: D000328:Adult; D005260:Female; D005947:Glucose / Q000378:metabolism; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008066:Lipolysis; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry; D009765:Obesity / Q000378:metabolism*; D012727:Sex Characteristics
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D005947:Glucose