title: Ghrelin stimulation of growth hormone isoforms: parallel secretion of total and 20-kDa growth hormone and relation to insulin sensitivity in healthy humans.
abstract: BACKGROUND
  The 20-kDa human GH (hGH) is produced in the pituitary by alternative splicing of the hGH-N gene. The 20-kDa hGH promotes growth similarly to 22-kDa or total hGH, the predominant form in circulation, but the relative effects of these isoforms on glucose metabolism have been debated.
  
  
  OBJECTIVE
  To investigate the effect of ghrelin on 20-kDa and total hGH secretion in healthy, nonobese subjects. We also studied associations between basal GH concentration and fasting glucose and insulin as well as between dynamic GH secretion and insulin sensitivity.
  
  
  METHODS
  Synthetic human acyl ghrelin (0.2 or 0.6 nmol/kg · h) or saline was infused in random order in 14 healthy subjects (six males, eight females; age 27.7 ± 6.3 yr; body mass index 22.0 ± 2.7 kg/m(2), mean ± SEM) on 3 separate days. Ghrelin was infused for 45 min to achieve steady-state levels and continued through a 3-h frequently sampled i.v. glucose tolerance test. Insulin sensitivity index was quantified using the minimal model of glucose kinetics.
  
  
  RESULTS
  Basal 20-kDa and total GH concentrations were 0.4 ± 0.1 and 2.2 ± 0.4 ng/ml, respectively, with a 20-kDa to total GH ratio of 0.13 ± 0.02. Females had significantly higher baseline GH levels. Ghrelin administration increased 20-kDa and total GH levels in a parallel and dose-dependent fashion, with no significant change in the ratio of the isoforms. Basal 20-kDa and total GH levels were negatively correlated with fasting glucose, insulin, and homeostasis model assessment of insulin resistance. During the frequently sampled iv glucose tolerance test, GH secretion was positively correlated with insulin sensitivity index with saline infusion.
  
  
  CONCLUSIONS
  Ghrelin dose-dependently increases endogenous 20-kDa and total GH secretion in a parallel fashion in healthy subjects. Both basal and stimulated levels of the different GH isoforms were positively associated with insulin sensitivity in this cohort of healthy men and women.
authors: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Cincinnati, Cincinnati, Ohio 45267, USA. jenny.tong@uc.edu
authors: Jenny
authors: J
authors: Tong
authors: David
authors: D
authors: D'Alessio
authors: Juliane
authors: J
authors: Ramisch
authors: Harold W
authors: HW
authors: Davis
authors: Elizabeth
authors: E
authors: Stambrook
authors: Matthias H
authors: MH
authors: Tschöp
authors: Martin
authors: M
authors: Bidlingmaier
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D054439:Ghrelin / Q000494:pharmacology*; D006706:Homeostasis; D019382:Human Growth Hormone / Q000096:biosynthesis* / Q000737:chemistry; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D007536:Isomerism; D049449:Luminescence; D008297:Male; D011863:Radioimmunoassay; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D054439:Ghrelin; D007328:Insulin; D019382:Human Growth Hormone