SYNERGISTIC EFFECT OF INSULIN-LIKE GROWTH FACTOR-I ADMINISTRATION ON THE PROTEIN-SPARING EFFECTS OF TOTAL PARENTERAL-NUTRITION IN FASTED LAMBS

Using primed constant isotopic infusions, we investigated the effects of recombinant human insulin-like growth factor-I (IGF-I) infusion on protein kinetics in both fasted and parenterally fed (TPN) lambs. Infusion of IGF-I at a dose of 50-mu-g/kg . h in fasted animals increased (P < 0.005) the mean plasma IGF-I concentration from 77.5 +/- 9.7 to 454.4 +/- 51.4 ng/ml. During IGF-I infusion the rate of net protein catabolism (NPC) was decreased (P < 0.005) by 17% from 3.5 +/- 0.2 to 2.9 +/- 0.2 g/kg . day, and the rate of appearance (Ra) of leucine in plasma decreased (P < 0.01) from 5.0 +/- 0.4 to 3.4 +/- 0.4-mu-mol/kg . min. In addition, the fractional synthetic rate of protein in cardiac and diaphragmatic muscle increased by 100% (P < 0.05) during the same period. After 3 h of TPN, the rate of NPC was decreased (P < 0.01) in the TPN animals compared to that in their fasted counterparts (1.89 +/-2.27 vs. 4.1 +/- 0.2 g/kg . day, respectively). The rate of NPC was further decreased after another 300 min of TPN to 0.76 +/- 0.27 g/kg . day. However, the Ra of leucine was not changed compared to the initial value. Infusion of IGF-I concurrently with TPN reversed (P <0.001) the rate of NPC from 1.02 +/- 0.21 g/kg . day after 180 min of TPN alone to a state of net protein gain of 0.14 +/- 0.19 g/kg . day after a further 300 min of combined IGF-I and TPN infusion. The Ra of leucine decreased (P < 0.01) from 3.9 +/- 0.8 to 2.5 +/- 0.47-mu-mol/kg . min during IGF-I and TPN infusion. Similarly, the fractional synthetic rates of protein in cardiac muscle, diaphragm, adductor muscle, psoas muscle, and hepatic tissue were increased (P < 0.05) compared to those in animals that received only TPN. The protein-sparing effects of IGF-I and TPN were synergistic, and the infusion of both agents resulted in the induction of a protein anabolic state within 60 min of commencing IGF-I infusion. In contrast, neither IGF-I nor TPN alone resulted in a state of net protein anabolism, and neither had an effect on protein kinetics until 120 min into the infusion. Consequently, IGF-I shows considerable potential as an anticatabolic agent when used synergistically with nutritional support.