Recombinant human insulin-like growth factor-I enhances whole body protein anabolism and significantly diminishes the protein catabolic effects of prednisone in humans without a diabetogenic effect.
To investigate whether recombinant human insulin-like growth factor-I (rhIGF-I) could serve as a protein-sparing nondiabetogenic agent, 21 healthy volunteers (mean age, 25 +/- 1 yr) were studied in 3 similar clinical models: rhIGF-I alone, rhIGF-I and prednisone, and prednisone alone. In study A, 6 subjects received infusions of [14C]leucine and [2H2]glucose before and after 5-7 days of rhIGF-I (100 micrograms/kg, sc, twice daily, followed by 16 h of a 10 micrograms/kg.h continuous sc infusion). The rate of appearance (Ra) of leucine, an estimate of whole body proteolysis, did not change significantly, whereas leucine oxidation decreased (-31 +/- 4%; P = 0.001), hence the nonoxidative leucine disposal (NOLD) increased significantly (P = 0.04). These effects are similar to those reported with high dose hGH. Plasma glucose concentrations did not change despite a significant reduction in circulating insulin concentrations (-58 +/- 11%; P = 0.01) and an increase in the glucose Ra (+12 +/- 5%; P = 0.04). After rhIGF-I treatment, plasma IGF-I, IGF-binding protein-1 (IGFBP-1), and IGFBP-2 all increased significantly, whereas IGFBP-3 did not change. In study B, seven subjects received rhIGF-I combined with oral prednisone (0.8 mg/kg.day) for 5 days. Group C (n = 8) received only prednisone. In group B, both the leucine Ra and oxidation increased (Ra, +7 +/- 3%; oxidation, +45 +/- 13%), but this increase was significantly less than that seen in group C (Ra, +25 +/- 5%; oxidation, 117 +/- 17%; P < 0.005 vs. group B). Group B showed no significant changes in postabsorptive glucose concentrations despite marked reductions in circulating insulin levels, in contrast to the increase in insulin and glucose concentrations observed in group C. In conclusion, 100 micrograms/g rhIGF-I, given twice daily, 1) has GH-like effects on whole body protein metabolism, 2) markedly diminishes the protein catabolic effect of glucocorticosteroids, and 3) is nondiabetogenic in prednisone-treated humans. This agent offers promise in the treatment of protein catabolic states.
Mauras
N
N
Nemours Children's Clinic, Jacksonville, Florida 32207.
Beaufrere
B
B
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis; D003920:Diabetes Mellitus / Q000139:chemically induced*; D005260:Female; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism; D008297:Male; D011241:Prednisone / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology
D001786:Blood Glucose; D002352:Carrier Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D011506:Proteins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D007930:Leucine; D011241:Prednisone