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 micrograms/kg.h in fasted animals increased (P less than 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 less than 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 less than 0.01) from 5.0 +/- 0.4 to 3.4 +/- 0.4 mumol/kg.min. In addition, the fractional synthetic rate of protein in cardiac and diaphragmatic muscle increased by 100% (P less than 0.05) during the same period. After 3 h of TPN, the rate of NPC was decreased (P less than 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 less than 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 less than 0.01) from 3.9 +/- 0.8 to 2.5 +/- 0.47 mumol/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 less than 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.