title: Insulin sensitivity and secretion influence the relationship between growth hormone-binding-protein and leptin.
abstract: BACKGROUND
  A direct relationship between body mass index (BMI), visceral adipose tissue, insulin levels and growth hormone-binding protein (GHBP) activity has consistently been reported. It was recently described that GHBP directly depends on serum leptin levels. Since leptin co-varies with insulin secretion and/or sensitivity, we aimed to study the influence of these variables on plasma GHBP activity.
  
  
  METHODS
  In order to isolate the effects of obesity per se from those of insulin secretion, three groups of subjects were prospectively studied: 14 lean, 10 obese and nine obese subjects with glucose intolerance.
  
  
  METHODS
  The percentage of body fat was measured through bioelectric impedance. Insulin sensitivity and secretion were determined through a frequently sampled intravenous glucose tolerance test with minimal model analysis. Serum leptin was measured by radioimmunoassay. GHBP activity was determined by the high performance liquid chromatography-gel filtration method.
  
  
  RESULTS
  Plasma GHBP activity was found to correlate with BMI (r = 0. 65, P < 0.0001), fat mass (r = 0.51, P = 0.003), waist circumference (r = 0.64, P < 0.0001), waist-to-hip ratio (r = 0.42, P = 0.01), insulin sensitivity (SI, r = - 0.61, P = 0.0001), insulin secretion (expressed as the acute insulin response to intravenous glucose, AIRg) (r = 0.48, P = 0.006) and leptin concentration (r = 0.49, P = 0.004). The associations with SI (r = - 0.42, P = 0.02) and AIRg (r = 0.38, P = 0.03) persisted even after controlling for fat mass. Since insulin secretion and insulin sensitivity usually covary in glucose tolerant subjects (an increased insulin secretion is necessary to compensate a decreased insulin sensitivity), we constructed a multiple linear regression to predict GHBP activity. In this model, SI (P = 0.005), AIRg (P = 0.02) and SD score-leptin (P = 0.03) independently contributed to 34, 10 and 8% of the variability in serum GHBP activity.
  
  
  CONCLUSIONS
  Our results suggest that plasma GHBP activity is simultaneouslly influenced by insulin secretion and sensitivity and leptin. Perhaps leptin, through increased insulin secretion, might induce GHBP/GH secretion, explaining the normal to high insulin-like growth factor (IGF)-I levels found in overnutrition.
authors.affiliation: Unitat de Diabetologia, Endocrinologia i Nutricio, University Hospital of Girona 'Dr Josep Trueta', Girona, Hormonal Laboratory, University Hospital 'Germans Trias i Pujol', Hormonal Laboratory, University Hospital Clinic, Barcelona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Fernandez-Real
authors.forename: M L
authors.initials: ML
authors.lastname: Granada
authors.forename: A
authors.initials: A
authors.lastname: Ruzafa
authors.forename: R
authors.initials: R
authors.lastname: Casamitjana
authors.forename: W
authors.initials: W
authors.lastname: Ricart
mesh_terms: D000328:Adult; D001824:Body Constitution / Q000502:physiology; D002352:Carrier Proteins / Q000097:blood*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D005260:Female; D018149:Glucose Intolerance; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D020738:Leptin / Q000097:blood*; D016014:Linear Models; D008297:Male; D009765:Obesity / Q000097:blood*; D011446:Prospective Studies
chemical_list: D002352:Carrier Proteins; D007328:Insulin; D020738:Leptin; C051815:somatotropin-binding protein