Effects of recombinant human insulin-like growth factor-I (rhIGF-I) on total and free IGF-I concentrations, IGF-binding proteins, and glycemic response in humans

Steven Lieberman, J. Bukar, S. A. Chen, A. C. Celniker, P. G. Compton, J. Cook, J. Albu, A. J. Perlman, A. R. Hoffman

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Abstract

To examine the effects of repeated administration of recombinant human insulin-like growth factor-I (rhIGF-I) on IGF-I levels, free IGF-I pharmacokinetics, glycemic response, and IGF-binding proteins (IGFBP), we administered rhIGF-I (0.03 mg/kg iv bolus) to 12 healthy males each morning for 5 consecutive days. Serum was collected over 24 h on days 1 and 5 for measurement of total and free IGF-I, glucose, insulin, and IGFBP. Total IGF-I was measured by RIA after acid/ ethanol extraction. Free IGF-I was separated from binding protein-complexed IGF-I using size exclusion high performance liquid chromatography before measurement by RIA. IGFBP were quantitated by optical densitometry of Western ligand blots. Total IGF-I increased significantly from 0-24 h after administration on day 1 (mean ± SD, μg/L: 120 ± 44 to 166 ± 51, P = 0.0002) but did not increase significantly from 24 h on day 1 to 0 h on day 5 (166 ± 51 to 178 ± 62) or from 0-24 h on day 5 (178 ± 62 to 209 ± 89). The area under the total IGF-I concentration curve was greater on day 5 than day 1 (311 ± 99 min·g/ L vs. 249 ± 77, P = 0.0001). There were no significant differences in free IGF-I concentration or pharmacokinetic parameters or in the degree or timing of hypoglycemia between days 1 and 5. Plasma insulin levels decreased significantly following rhIGF-I administration (day 1 baseline: 53 ± 11 pmol/L, nadir: 18 ± 6 pmol/L at 30 min, P = 0.003); day 5 baseline: 47 ± 15 pmol/L, nadir: 16 ± 8 pmol/L at 30 min, P = 0.0003). Western ligand blotting revealed the transient appearance of a 30-kilodalton band which migrates in a manner similar to IGFBP-1. This band was undetectable at baseline, peaked between 150 and 210 min after rhIGF-I administration, and diminished by 480-600 min The response was similar on days 1 and 5. There were no substantial changes in the serum levels of any other IGFBP. In summary, repeated iv bolus administration of rhIGF-I increased the level of total circulating IGF-I without changing free IGF-I disposition or glycemic response A 30-kilodalton IGFBP band, most likely IGFBP-1, appeared transiently following rhIGF-I administration, probably as a result of suppression of insulin levels. IGFBP-2, -3, and -4 were unaffected.

Original languageEnglish (US)
Pages (from-to)30-36
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume75
Issue number1
StatePublished - Jul 1992
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Lieberman, S., Bukar, J., Chen, S. A., Celniker, A. C., Compton, P. G., Cook, J., Albu, J., Perlman, A. J., & Hoffman, A. R. (1992). Effects of recombinant human insulin-like growth factor-I (rhIGF-I) on total and free IGF-I concentrations, IGF-binding proteins, and glycemic response in humans. Journal of Clinical Endocrinology and Metabolism, 75(1), 30-36.