Greater potency of IGF-I than IGF-I/BP-3 complex in catabolic parenterallyfed rats

We compared the anabolic effects of recombinant human insulin-like growth f actor I (rhIGF-I, 2.5 mg/kg) and equimolar amounts of rhIGF-I prebound to r hIGF binding protein-3 (rhIGF-I/BP-3) coinfused continuously with total par enteral nutrition (TPN) solution in dexamethasone (Dex, 70 mu g/day ip)-tre ated male rats for 6 days. The four TPN groups included control, Dex, Dex IGF-I, and Dex + IGF-I/BP-3. Pharmacokinetic analysis indicated reduced cl earance of IGF-I when infused as IGF-I/BP-3 compared with free IGF-I(0.91 /- 0.09 vs. 2.01 +/- 0.19 ml serum/min, P < 0.001) and this was associated with significantly greater serum IGF-I concentrations in the Dex + IGF-I/BP -3 group. Despite greater total serum IGF-I levels, infusion of free IGF-I produced greater anabolic responses than IGF-I/BP-3 based on body weight, n itrogen balance, and jejunal cellularity. Treatment with free IGF-I, but no t IGF-I/BP-3, significantly reduced serum insulin and glucose levels that w ere elevated due to Dex. There mere no significant differences in Liver IGF -I mRNA levels between groups. Serum IGFBP-3 levels were elevated with infu sion of IGF-I/BP-3 compared with IGF-I. These results indicate greater anab olic potency of IGF-I compared with IGF-I/BP-3 when administered by continu ous parenteral infusion with TPN solution in catabolic rats.