Proteolysis of insulin-like growth factor-binding protein-3 in human immunodeficiency virus-positive children who fail to thrive

Robert A. Frost, Sharon A. Nachman, Charles H. Lang, Marie C. Gelato

Research output: Contribution to journalArticle

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Abstract

Failure to thrive is a common manifestation of human immunodeficiency virus (HIV) infection in children. Given the role of insulin-like growth factor I (IGF-I) in stimulating postnatal growth, we have examined whether HIV-infected pediatric patients with growth failure have lower serum concentrations of IGF-I than age-matched control subjects. IGF-I was measured in 16 HIV-infected children and 13 HIV-negative controls. Ten of the HIV- infected children failed to thrive based on height and linear growth that was below the National Center for Health Statistics 10th percentile. IGF-I levels were significantly lower in children who failed to thrive compared to those in age-matched controls (20 vs. 60 μg/L; P < 0.001). Children who failed to thrive also displayed lower IGF-I levels than HIV-positive children, who exhibited normal growth velocity (20 vs. 91 μg/L; P < 0.001). Failure to thrive was associated with a significant reduction in circulating levels of IGF-binding protein-3 (IGFBP-3), as determined by ligand and Western blotting (P < 0.001), enhanced IGFBP-3 proteolysis (P < 0.001), and a decrease in the serum concentration of the acid-labile subunit of the IGFBP-3 ternary complex (P < 0.005). IGFBP-3 proteolysis was negatively correlated with IGF-I (r = 0.78) and IGFBP-3 levels (r = 0.70). Failure to thrive was associated with a reduction in the formation of the ternary complex, but the ternary complex could be restored by the addition of an excess of IGFBP-3 to serum. These results indicate that low levels of IGF-I, IGFBP-3, and acid-labile subunit are associated with a failure to thrive in HIV-infected children.

Original languageEnglish (US)
Pages (from-to)2957-2962
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume81
Issue number8
DOIs
StatePublished - Oct 8 1996

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Proteolysis
Insulin-Like Growth Factor Binding Protein 3
Insulin-Like Growth Factor I
Viruses
Failure to Thrive
HIV
Growth
Serum
National Center for Health Statistics (U.S.)
Pediatrics
Acids
Virus Diseases
human IGFBP3 protein
Western Blotting
Health
Statistics
Ligands

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

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abstract = "Failure to thrive is a common manifestation of human immunodeficiency virus (HIV) infection in children. Given the role of insulin-like growth factor I (IGF-I) in stimulating postnatal growth, we have examined whether HIV-infected pediatric patients with growth failure have lower serum concentrations of IGF-I than age-matched control subjects. IGF-I was measured in 16 HIV-infected children and 13 HIV-negative controls. Ten of the HIV- infected children failed to thrive based on height and linear growth that was below the National Center for Health Statistics 10th percentile. IGF-I levels were significantly lower in children who failed to thrive compared to those in age-matched controls (20 vs. 60 μg/L; P < 0.001). Children who failed to thrive also displayed lower IGF-I levels than HIV-positive children, who exhibited normal growth velocity (20 vs. 91 μg/L; P < 0.001). Failure to thrive was associated with a significant reduction in circulating levels of IGF-binding protein-3 (IGFBP-3), as determined by ligand and Western blotting (P < 0.001), enhanced IGFBP-3 proteolysis (P < 0.001), and a decrease in the serum concentration of the acid-labile subunit of the IGFBP-3 ternary complex (P < 0.005). IGFBP-3 proteolysis was negatively correlated with IGF-I (r = 0.78) and IGFBP-3 levels (r = 0.70). Failure to thrive was associated with a reduction in the formation of the ternary complex, but the ternary complex could be restored by the addition of an excess of IGFBP-3 to serum. These results indicate that low levels of IGF-I, IGFBP-3, and acid-labile subunit are associated with a failure to thrive in HIV-infected children.",
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Proteolysis of insulin-like growth factor-binding protein-3 in human immunodeficiency virus-positive children who fail to thrive. / Frost, Robert A.; Nachman, Sharon A.; Lang, Charles H.; Gelato, Marie C.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 81, No. 8, 08.10.1996, p. 2957-2962.

Research output: Contribution to journalArticle

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AU - Nachman, Sharon A.

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