Comparison of the effects of human recombinant insulin-like growth factor I and insulin on plasma amino acid concentrations and leucine kinetics in humans

Abstract

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/l) 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 Μmol/l) and total branched chain amino acids (BCAA) declined by 34±3% (390±21 to 256±13 Μmol/l). This hypoaminoacidaemic effect was associated with a decline in endogenous leucine flux of 17±2% (1.88±0.05 to 1.57±0.04 Μmol·kg−1·min−1) and leucine oxidation of 17±1% (0.31±0.02 vs 0.26±0.02 Μmol·kg−1·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−1·min−1 to obtain a steady-state plasma insulin concentration of 530±25 pmol/l 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·kg−1 ·min−1, respectively. During insulin infusion total BCAA declined by 39% from 369±23 to 226±20 Μmol/l, leucine flux declined by 16±2% from 1.90±0.05 to 1.61±0.03 Μmol·kg−1·min−1, and leucine oxidation declined by 19±2% from 0.32±0.02 to 0.26±0.02 Μmol·kg−1·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.