Inhibition of the Action of Nonsuppressible Insulin-Like Activity on Isolated Rat Fat Cells by Binding to its Carrier Protein

Zapf, J.; Schoenle, Eugen J.; Jagars, G.; Sand, I. Charles; Grünwald, J.; Froesch, E. R.

doi:10.1172/jci109377

Cited by 177 publications

(46 citation statements)

References 36 publications

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“…The apparently elevated levels of IGF-I in the unextracted sera of cancer patients were clearly due to BP effects as evidenced by the detection of IGF-I binding proteins in cancer patient serum fractions having reactivity in the Amersham RIA and by the results obtained for extracted sera. The observation that serum levels of IGF-I are not increased in SCLC patients, though consistent with those of earlier reports (Minuto et al, 1986;Macaulay et al, 1988b), is perhaps surprising given the over-production of BPs in lung cancer patients and the ability of BPs to prolong the half life of IGFs in the circulation (Cohen & Nissley, 1976;Zapf et al, 1979). One explanation is that the release of IGF-I from SCLC cells in vivo is, like IGF-I release from liver, hormonally regulated by mechanisms which do not exist in vitro.…”

Section: Detection Of Immunoreactive Igf-i In Cell Conditioned Mediasupporting

confidence: 85%

Production of immunoreactive insulin-like growth factor-I (IGF-I) and IGF-I binding proteins by human lung tumours

Reeve

Payne²,

Bleehen³

1990

Br J Cancer

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Summary The production of insulin-like growth factor I (IGF-I) and IGF-I binding proteins (BPs) by human lung tumour cell lines in vitro has been examined and the levels of these substances in the serum of lung cancer patients investigated. While small cell lung cancer (SCLC) cell lines secreted both IGF-I and BPs, non-small cell lung cancer (NSCLC) cell lines secreted BPs only. No evidence of increased serum IGF-I levels was obtained in a cohort of 52 lung cancer patients having SCLC and NSCLC histologies. In contrast, serum levels of low molecular weight BPs were markedly elevated in the majority of lung cancer patients.The detection of elevated immunoreactive insulin-like growth factor-I (IGF-I) in human lung tumours (Minuto et al., 1986;Macaulay et al., 1988a) Healthy adult male and female non-smokers (n = 32), and male and female normal smokers (n = 31) were included in the study as controls. The age range for controls was 23-81 years and for lung cancer patients 39-79 years.Pre-treatment serum samples were prepared immediately after collection and stored at -70'C before assay. IGF-I determinationsA radioimmunoassay (RIA) kit (Amersham International, Aylesbury, UK) and a somatomedin C (SM-C) immunoradiometric (IRMA) kit (Immunodiagnostics Ltd, Tyne and Wear, UK) were used for the quantitative measurement of IGF-I in conditioned media and serum samples. Recombinant human IGF-I was used as standards in both assays. The rabbit antiserum used in the competitive RIA was raised against a recombinant analogue of IGF-I, shows 100% cross-reactivity with human IGF-I and 0.5% crossreactivity with human IGF-II. Fifty per cent displacement of tracer occurs with insulin at 2,000 ftunits ml-' (normal range of insulin in fasting individuals is 4-30 gunits ml-' in serum). Phase separation was achieved using Amerlex-M donkey anti-rabbit reagent (Amersham UK). Assay sensitivity is 100pg per tube.The non-competitive SM-C IRMA employed a two site immunoradiometric assay. Briefly standards/samples were incubated simultaneously with a mouse monoclonal anti-SM-C lgG immobilised on the inside walls of test tubes and a '25I-labelled mouse monoclonal antibody directed against a second IGF-I epitope. Unbound materials were then removed by decanting and washing the tubes. The antisera show 3% cross-reactivity with IGF-II and did not cross-react at all with insulin or pro-insulin. The lowest detectable level of SM-C that could be distinguished from the zero standard was 8 mU ml' at the 95% confidence limit.To separate binding protein from IGF-I, serum samples and cell conditioned media were extracted by incubation in 50 of acid extraction solution (supplied by Immunodiagnostics Ltd) for 10min at room temperature. Neutralising solution (500pl) (supplied by Immunodiagnostics Ltd) was then added to each sample. This extraction procedure yields aproximately 100% recovery of SM-C in patient samples. The neutralised, extracted conditioned media and serum samples, and unextracted serum samples were then used in the Amersham RIA and the IRMA.

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Section: Detection Of Immunoreactive Igf-i In Cell Conditioned Mediasupporting

confidence: 85%

Production of immunoreactive insulin-like growth factor-I (IGF-I) and IGF-I binding proteins by human lung tumours

Reeve

Payne²,

Bleehen³

1990

Br J Cancer

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“…The initial interpretation of the function of such binding proteins was that they would prolong the half-life of the IGFs in the circulation and inhibit their metabolic effects by preventing them from binding to the receptors (Zapf et al 1979), which would be an essential property as the IGFs are also able to interact with the insulin receptor and are present in serum at a concentration 1000 times higher than that of insulin (Daughaday & Rotwein 1989). Intense research in this area led to the sequential discovery of six different IGF-binding proteins (IGFBPs).…”

Section: Introductionmentioning

confidence: 99%

IGF-binding protein-5: flexible player in the IGF system and effector on its own

Schneider¹,

Wolf²,

Hoeflich³

et al. 2002

Journal of Endocrinology

160

137

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The multiple activities of IGF-I and -II are modulated by a family of IGF-binding proteins (IGFBP-1 to -6). Although structurally related, each IGFBP has unique properties and exerts specific functions. IGFBP-5 is the most conserved IGFBP across species and was identified as an essential regulator of physiological processes in bone, kidney and mammary gland. In addition, IGFBP-5 appears to play a decisive role in the control of proliferation of specific tumour cell types. In many situations IGFBP-5 exerts biological activities in the absence of IGFs, indicating the existence of IGF-independent actions. This concept was supported by the unexpected localisation of IGFBP-5 in the nucleus and the description of IGFBP-5-specific membrane-bound IGFBP-5 receptor(s). The scope of this review is to summarise the available information about the structure of IGFBP-5 and the regulation of its expression. Furthermore, the potential significance of IGFBP-5 in the regulation of physiological processes will be critically analysed in the light of recent experimental data.

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“…In various bioassays partly purified BP fractions were shown to inhibit the insulin-like and growth-promoting activities of IGF (Drop et al, 1979;Zapf et al, 1979). In vivo the BPs increase the biological half-life of IGFs (Hintz, 1984).…”

Section: Introductionmentioning

confidence: 99%

Isolation and characterization of a cDNA encoding the low molecular weight insulin-like growth factor binding protein (IBP-1).

et al. 1988

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IGF‐I and IGF‐II are growth‐stimulating peptides with strong mitogenic properties. These polypeptide growth factors circulate in serum bound to specific binding proteins. We report the cloning and complete sequence of a cDNA encoding a low mol. wt IGF‐binding protein from a human placenta cDNA library. We propose the designation IGF‐binding protein 1 (IBP‐1) for the gene and corresponding protein. Expression of the cDNA encoding IBP‐1 in COS cells resulted in the synthesis of a 30‐kd protein which binds IGF‐I and is immunologically indistinguishable from the IGF‐binding protein isolated from amniotic fluid or human serum. Northern blotting analysis demonstrated that expression of the IBP‐1 gene is highly tissue specific and limited to placental membranes and fetal liver suggesting a rigid control. The IBP‐1 gene is a single copy gene, located on chromosome 7. The results obtained suggest that most, if not all, lower mol. wt IGF‐binding proteins originate from this gene.

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Inhibition of the Action of Nonsuppressible Insulin-Like Activity on Isolated Rat Fat Cells by Binding to its Carrier Protein

Cited by 177 publications

References 36 publications

Production of immunoreactive insulin-like growth factor-I (IGF-I) and IGF-I binding proteins by human lung tumours

Production of immunoreactive insulin-like growth factor-I (IGF-I) and IGF-I binding proteins by human lung tumours

IGF-binding protein-5: flexible player in the IGF system and effector on its own

Isolation and characterization of a cDNA encoding the low molecular weight insulin-like growth factor binding protein (IBP-1).

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