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Am J Physiol Endocrinol Metab 272: E628-E633, 1997;
0193-1849/97 $5.00
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AJP - Endocrinology and Metabolism, Vol 272, Issue 4 E628-E633, Copyright © 1997 by American Physiological Society

ARTICLES

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

N. Mauras, P. M. Martha Jr, V. Quarmby and M. W. Haymond
Nemours Children's Clinic, Jacksonville, Florida 32207, USA.

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.


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