rhIGF-I administration in humans: differential metabolic effects of bolus vs. continuous subcutaneous delivery

Am J Physiol. 1997 Apr;272(4 Pt 1):E628-33. doi: 10.1152/ajpendo.1997.272.4.E628.


The metabolic effects of recombinant human insulin-like growth factor I (rhIGF-I) were compared using bolus vs. continuous subcutaneous infusions. Subjects (n = 5, 29 +/- 3 yr) received rhIGF-I as subcutaneous infusions by a Minimed pump (200 microg x kg(-1) x day(-1) over 16 h/day), and their data were compared with those of subjects (n = 6, 24 +/- 2 yr) who received subcutaneous 200 microg x kg(-1) x day(-1) injections twice a day. L-[1-14C]leucine and [6,6-2H2]glucose infusion studies and indirect calorimetry were performed, and total and free IGF-I, insulin, and glucose concentrations were measured before and after 5-7 days of rhIGF-I. Estimates of protein breakdown, oxidation, and synthesis did not change after pump therapy; in contrast, after bolus doses, protein oxidation decreased (P = 0.001) and whole body protein synthesis increased (P = 0.04). There was no change in lipid oxidation after pump treatment, whereas the bolus group had lower lipid oxidation (P = 0.035). Both treatment modalities increased glucose oxidation (P < 0.02) and glucose production rates (P < 0.03). Overnight fasting insulin concentrations decreased in both groups, whereas plasma glucose remained invariant in the bolus group and decreased modestly in the pump group. Total IGF-I concentrations increased comparably in both groups, but the increase in free IGF-I was greater in the bolus-treated group (P = 0.001). We conclude that, in GH-sufficient postabsorptive individuals, the metabolic effects of rhIGF-I are in part dependent on the mode of administration, with a robust protein-anabolic effect when rhIGF-I is given as twice daily bolus injections but no detectable effect on protein turnover after a continuous mode of delivery. There were higher free IGF-I levels in the bolus-treated subjects, suggesting that this form of the molecule may be important for mediating IGF-I's protein-anabolic effects at the tissue level. The data also suggest that carbohydrate metabolism is more responsive than protein metabolism to the continuous subcutaneous modality of rhIGF-I administration. Even though the mechanism of these differences in metabolic effects is not entirely clear, it should be taken into account when patients are given rhIGF-I as prolonged treatment.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Calorimetry, Indirect
  • Energy Metabolism / drug effects
  • Female
  • Glucose / metabolism
  • Humans
  • Infusion Pumps
  • Injections, Subcutaneous
  • Insulin-Like Growth Factor Binding Proteins / blood
  • Insulin-Like Growth Factor I / administration & dosage*
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / pharmacology
  • Insulin-Like Growth Factor II / metabolism
  • Kinetics
  • Leucine / metabolism
  • Male
  • Metabolism / drug effects*
  • Oxidation-Reduction / drug effects
  • Recombinant Proteins


  • Insulin-Like Growth Factor Binding Proteins
  • Recombinant Proteins
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • Leucine
  • Glucose