A low dose euglycemic infusion of recombinant human insulin-like growth factor I rapidly suppresses fasting-enhanced pulsatile growth hormone secretion in humans.
To determine if insulin-like growth factor I (IGF-I) inhibits pulsatile growth hormone (GH) secretion in man, recombinant human IGF-I (rhIGF-I) was infused for 6 h at 10 micrograms.kg-1.h-1 during a euglycemic clamp in 10 normal men who were fasted for 32 h to enhance GH secretion. Saline alone was infused during an otherwise identical second admission as a control. As a result of rhIGF-I infusion, total and free IGF-I concentrations increased three- and fourfold, respectively. Mean GH concentrations fell from 6.3 +/- 1.6 to 0.59 +/- 0.07 micrograms/liter after 120 min. GH secretion rates, calculated by a deconvolution algorithm, decreased with a t 1/2 of 16.6 min and remained suppressed thereafter. Suppression of GH secretion rates occurred within 60 min when total and free IGF-I concentrations were 1.6-fold and 2-fold above baseline levels, respectively, and while glucose infusion rates were < 1 mumol.kg-1.min-1. During saline infusion, GH secretion rates remained elevated. Infusion of rhIGF-I decreased the mass of GH secreted per pulse by 84% (P < 0.01) and the number of detectable GH secretory pulses by 32% (P < 0.05). Plasma insulin and glucagon decreased to nearly undetectable levels after 60 min of rhIGF-I. Serum free fatty acids, beta-hydroxybutyrate, and acetoacetate were unaffected during the first 3 h of rhIGF-I but decreased thereafter to 52, 32, and 50% of levels observed during saline. We conclude that fasting-enhanced GH secretion is rapidly suppressed by a low-dose euglycemic infusion of rhIGF-I. This effect of rhIGF-I is likely mediated through IGF-I receptors independently of its insulin-like metabolic actions.
Department of Medicine, University of Virginia Health Sciences Center, Charlottesville 22908.
M L
ML
Hartman
P E
PE
Clayton
M L
ML
Johnson
A
A
Celniker
A J
AJ
Perlman
K G
KG
Alberti
M O
MO
Thorner
D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000097:blood; D000328:Adult; D001693:Biological Transport, Active / Q000187:drug effects; D005215:Fasting / Q000502:physiology*; D005227:Fatty Acids / Q000097:blood; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D010507:Periodicity; D011994:Recombinant Proteins / Q000494:pharmacology
D000090:Acetoacetates; D005227:Fatty Acids; D006885:Hydroxybutyrates; D007328:Insulin; D011994:Recombinant Proteins; C016635:acetoacetic acid; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D005934:Glucagon; D020155:3-Hydroxybutyric Acid