title: Insulin infusion reduces hepatocyte growth factor in lean humans.
abstract: OBJECTIVE
  Plasma Hepatocyte Growth Factor (HGF) is significantly elevated in obesity and may contribute to vascular disease, metabolic syndrome or cancer in obese individuals. The current studies were done to determine if hyperinsulinemia increases plasma HGF.
  
  
  METHODS
  Twenty-two participants (10 women/12 men, BMI 20.6-34.5 kg/m(2), age 18-49 years) underwent a hyperinsulinemic euglycemic clamp with measurement of HGF at baseline and steady state. Relationships between baseline HGF, anthropometrics, triglycerides, liver enzymes, c-reactive protein and adiponectin were also evaluated.
  
  
  RESULTS
  Fasting HGF was positively correlated (P<0.050) with weight (r=0.63), BMI (r=0.55), waist circumference (r=0.68), WHR (r=0.48), triglycerides (r=0.44), alanine aminotransferase (r=0.74) and γ-glutamyl transpeptidase (r=0.56), but not c-reactive protein or adiponectin. In stepwise regression, alanine aminotransferase and insulin sensitivity accounted for significant variation in fasting HGF. A significant effect of insulin to suppress HGF during the clamp (P=0.029) was found after adjustment for BMI. HGF was reduced 7% at steady state in the lean subjects only (437.1 ±57.8 vs 405.4±72.0 pg/ml; P=0.030).
  
  
  CONCLUSIONS
  The positive correlation of HGF with hepatic enzymes suggests liver may be a significant source of circulating HGF in lean subjects. The strong correlation of plasma HGF with adiposity and the lack of an effect of insulin to increase HGF during the clamp in obese subjects suggest that adiposity, rather than elevated insulin levels, may be the major contributor to plasma HGF in obese subjects. Thus, a reduction in plasma HGF through weight loss is likely the best way to decrease comorbidities mediated by this angiogenic and mitogenic factor.
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Barbora
authors.initials: B
authors.lastname: de Courten
authors.forename: Maximilian P J
authors.initials: MP
authors.lastname: de Courten
authors.forename: Sonia
authors.initials: S
authors.lastname: Dougherty
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Forbes
authors.forename: Jenna R
authors.initials: JR
authors.lastname: Potts
authors.forename: Robert V
authors.initials: RV
authors.lastname: Considine
mesh_terms: D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015309:Glucose Clamp Technique; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006801:Humans; D007260:Infusion Pumps; D007328:Insulin / Q000008:administration & dosage*; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D013851:Thinness / Q000097:blood*; D055815:Young Adult
chemical_list: D007328:Insulin; D017228:Hepatocyte Growth Factor