RGD Reference Report - Uptake of circulating insulin-like growth factors (IGFs) into cerebrospinal fluid appears to be independent of the IGF receptors as well as IGF-binding proteins. - Rat Genome Database

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Uptake of circulating insulin-like growth factors (IGFs) into cerebrospinal fluid appears to be independent of the IGF receptors as well as IGF-binding proteins.

Authors: Pulford, BE  Ishii, DN 
Citation: Pulford BE and Ishii DN, Endocrinology 2001 Jan;142(1):213-20.
RGD ID: 61526
Web Url: http://endo.endojournals.org/cgi/content/full/142/1/213
Pubmed: PMID:11145584   (View Abstract at PubMed)
DOI: DOI:10.1210/endo.142.1.7894   (Journal Full-text)

Peripheral administration of human insulin-like growth factor (hIGF) results in both uptake of hIGF into the cerebrospinal fluid (CSF) and amelioration of brain injury. We tested the hypotheses that IGF uptake into CSF is independent of IGF receptors and IGF-binding proteins (IGFBP). Adult rats were injected sc with various concentrations of hIGF-I or structural analogs, and serum and CSF were withdrawn for assay 90 min later. An enzyme-linked immunoassay was used that detected immunoreactive hIGF-I and its analogs, but not rat IGF-I, IGF-II, or insulin. Plasma hIGF-I levels increased linearly (r = 0.97) with hIGF-I dose between 25-300 microgram/rat. By contrast, uptake into CSF reached saturation above 100 microgram, suggesting carrier-mediated uptake. hIGF-II reduced the uptake of hIGF-I into CSF (P < 0.02). Des(1-3)hIGF-I is a hIGF-I analog missing the N-terminal tripeptide, resulting in greatly reduced affinity for IGFBP-1, -3, -4, and -5. Nevertheless, des(1-3)hIGF-I was taken up into CSF. [Leu(24)]hIGF-I and [Leu(60)]hIGF-I have 20- to 85-fold reduced affinity for the type I IGF receptor, yet both were taken up into CSF in amounts similar to hIGF-I. In addition, hIGF-I and des(1-3)hIGF-I were taken up into CSF, although binding to the type II receptor is extremely weak. These data suggest that uptake of circulating IGF-I into CSF is independent of the type I or II IGF receptors as well as IGF sequestration to IGFBP-1, -3, -4, or -5.

Objects referenced in this article
Gene Igf1r insulin-like growth factor 1 receptor Rattus norvegicus
Gene Igfbp1 insulin-like growth factor binding protein 1 Rattus norvegicus

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