A Low Dose Euglycemic Infusion of Recombinant Human Insulin - like Growth Factor I Rapidly Suppresses Fasting - enhanced

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 ,ug * kg-' * hduring 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 threeand fourfold, respectively. Mean GH concentrations fell from 6.3±1.6 to 0.59±0.07 ,g/liter after 120 min. GH secretion rates, calculated by a deconvolution algorithm, decreased with a t1/2 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 ,umol kg-' * min-'. During saline infusion, GH secretion rates remained elevated. Infusion of rhIGFI 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, jl-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. (J. Clin. Invest. 1993. 91:2453-2462.)