We examined the effects of recombinant human insulin-like growth factor I (IGF-I) and insulin on the plasma amino acid (AA) profile and leucine kinetics in eight normal subjects. IGF-I was infused at 52 pmol. kg -1. min -1, in combination with prime-continuous [1-14C] leucine infusion, to obtain steady-state plasma concentrations of total (54 + 3 nmol/1) and free (7.3 + 1 nmol/l) IGF-I (study 1). In response to IGF-I, plasma AA levels declined by 37 + 3 % (1975 + 198 to 1368 + 120 ~mol/1) and total branched chain amino acids (BCAA) declined by 34 + 3 % (390 + 21 to 256 + 13 ~mol/1). This hypoaminoacidaemic effect was associated with a decline in endogenous leucine flux of 17 + 2 % (1.88 + 0.05 to 1.57 + 0.04 9tool. kg -1 9 min -1) and leucine oxidation of 17 + 1% (0.31 + 0.02 vs 0.26 + 0.02 pmol. kg -1 9 min -1) (both p < 0.01 vs basal). The same subjects underwent a second study (study 2) in which insulin was infused at 6.22 pmol -kg -~ 9 min -1 to obtain a steady-state plasma insulin concentration of 530 + 25 pmol/1 while maintaining euglycaemia. The infusion rate was designed to match the declines in plasma BCAA levels and leucine turnover observed during IGF-I infusion. The rates of glucose infusion necessary to maintain euglycaemia during IGF-I and insulin infusion were 4.9 + 1.0 and 7.8 + 0.6 mg 9 kg -1 9 rain -1, respectively. During insulin infusion total BCAA declined by 39% from 369_+23 to 226 + 20 ~tmol/l, leucine flux declined by 16 + 2 % from 1.90 + 0.05 to 1.61 + 0.03 ~mol. kg -1 9 min -1, and leucine oxidation declined by 19 + 2% from 0.32 + 0.02 to 0.26 + 0.02 ~mol -kg -1 9 min -1. On a molar basis IGF-I was 7.3 % as potent as insulin in inhibiting proteolysis. These results demonstrate that in humans: (i) the hypoaminoacidaemic response to IGF-I can be entirely ascribed to the inhibition of proteolysis; (ii) qualitatively, the effects of IGF-I and insulin on plasma AA profile and protein metabolism are similar; (iii) quantitatively, IGF-I is 14-fold less potent than insulin in suppressing protein degradation. [Diabetologia (1995) 38: 732-738] Key words Leucine, ketoisocaproate, insulin, IGF-I, protein metabolism.
Insulin-like growth factor (IGF-I) is a growth promoting peptide that shares considerable structural homology with insulin [1]. It induces cellular growth