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Ghrelin stimulation of growth hormone isoforms: Parallel secretion of total and 20-kDag growth hormone and relation to insulin sensitivity in healthy humans.
J. Clin. Endocrinol. Metab. 97, 3366-3374 (2012)
Context: 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. Design and Setting: 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 iv 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. Conclusion: 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. (J Clin Endocrinol Metab 97: 3366-3374, 2012)
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
BETA-CELL FUNCTION; STRUCTURAL VARIANT; HYPERGLYCEMIC ACTIVITY; GLUCOSE-TOLERANCE; HGH DIFFERS; 22-KDA HGH; 20K HGH; GH; METABOLISM; RATS
ISSN (print) / ISBN
0021-972X
e-ISSN
1945-7197
Quellenangaben
Volume: 97,
Issue: 9,
Pages: 3366-3374
Publisher
Endocrine Society
Publishing Place
Bethesda, Md.
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Obesity (IDO)