Insulinlike Growth Factor-Binding Proteins

Rosenfeld, Ron G.; Lamson, George; Pham, Hung; Oh, Youngman; Conover, Cheryl A.; León, Daisy De; Donovan, Sharon M.; Ocrant, Ian; Giudice, Linda C.

doi:10.1016/b978-0-12-571146-3.50009-2

Cited by 144 publications

(62 citation statements)

References 166 publications

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“…It has been accepted dogma that, unlike insulin, the IGFs bind to a family of binding proteins (IGFBPs) with high affinity and specificity (3)(4)(5). The six well characterized IGFBPs have significant sequence homology, including a GCGCCXXC motif as part of 10 -12 conserved cysteines at the amino terminus and six conserved cysteines at the carboxyl terminus.…”

mentioning

confidence: 99%

Inhibition of Insulin Receptor Activation by Insulin-like Growth Factor Binding Proteins

Yamanaka¹,

Wilson

Rosenfeld

et al. 1997

Journal of Biological Chemistry

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), also binds insulin with high affinity and blocks insulin action. IGFBPs with enhanced affinity for insulin might contribute to the insulin resistance of pregnancy, type II diabetes mellitus, and other pathological conditions.Insulin-like growth factors (IGFs)-I 1 and -II are structurally related to insulin, sharing approximately 50% amino acid homology with insulin in the A-and B-chain regions but retaining a connecting peptide, as well as a carboxyl-terminal extension (1). The anabolic and mitogenic actions of IGFs are mediated largely through the type 1 IGF receptor, which, like the insulin receptor, is a heterotetrameric, membrane-spanning tyrosine kinase (2).It has been accepted dogma that, unlike insulin, the IGFs bind to a family of binding proteins (IGFBPs) with high affinity and specificity (3-5). The six well characterized IGFBPs have significant sequence homology, including a GCGCCXXC motif as part of 10 -12 conserved cysteines at the amino terminus and six conserved cysteines at the carboxyl terminus. We have recently characterized two additional secreted proteins with lower affinity for IGFs (IGFBP-7/mac25 and IGFBP-8/CTGF) and two additional potential members of the IGFBP superfamily (6 -9). The structure of IGFBP-7 revealed the presence of amino-terminal conserved sequences, including 11 cysteines, but lower sequence homology in the normally well-conserved COOH terminus. IGFBPs 1-6 are believed to function as carrier proteins for IGFs, delaying degradation of IGF peptides and increasing their half-lives and inhibiting IGF access to receptors (10 -14).Proteolysis of IGFBPs, as observed during pregnancy, results in IGFBP fragments with decreased affinity for IGFs and, thereby, promotes enhanced access of IGFs to their receptors (15,16). Recent studies have demonstrated that several of these IGFBPs, especially IGFBP-3, may also be capable of directly inhibiting cell growth in an IGF-independent manner (17-23). Both intact IGFBP-3 and IGFBP-3 proteolytic fragments have been shown to be capable of blocking the mitogenic effect of insulin (24,25). Whether these effects reflect inhibition of insulin signaling pathways or a direct effect of IGFBP-3 and its fragments on cell growth remains unclear.We have, therefore, reevaluated the ability of IGFBPs 1-6, IGFBP-7, and IGFBP-3 proteolytic fragments to bind insulin and have demonstrated that IGFBP-7 and NH 2 -terminal fragment of IGFBP-3 (IGFBP-3 ) not only bind insulin specifically but also modulate insulin binding to its receptor and subsequently inhibiting insulin-stimulated autophosphorylation of the insulin receptor ␤ subunit and phosphorylation of IRS-1. EXPERIMENTAL PROCEDURESMaterials-High performance liquid chromatography-purified hIG-FBP-1 from human amniotic fluid was kindly provided by Dr. D. R. Powell (Baylor College of Medicine, Houston, TX) (26). Recombinant human IGFBP-3 (rhIGFBP-3), a nonglycosylated 29 kDa core protein expressed in Escherichia coli cells, was the generous gift of Celtrix, Inc. (Santa Clara, CA) (27). Recombinant human IG...

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mentioning

confidence: 99%

Inhibition of Insulin Receptor Activation by Insulin-like Growth Factor Binding Proteins

Yamanaka¹,

Wilson

Rosenfeld

et al. 1997

Journal of Biological Chemistry

Self Cite

189

155

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“…8 While all IGFBPs (IGFBP1-IGFBP7) are structurally related, their functions are non-redundant from each other and they exert their effects also independently from IGF. [9][10][11] IGFBPs have been linked to several human disorders, such as different growth disorders 12,13 and insulin resistance. 14 IGFBP3 is the major circulating IGFBP, which binds 75% of IGFs in healthy people, forming 140 kDa complexes.…”

Section: Introductionmentioning

confidence: 99%

Association of sequence variations in the gene encoding insulin-like growth factor binding protein 5 with adiponectin

Kallio

Kolehmainen

et al. 2008

Int J Obes

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Background: Insulin-like growth factor binding protein 5 (IGFBP5) binds to IGF and thus modulates IGF signaling pathway. We have shown earlier that the IGFBP5 gene was downregulated in the adipose tissue after 12-week carbohydrate diet with low insulinemic response. Objective: The aim was to examine the putative contribution of genetic variation of the IGFBP5 gene to the characteristics of metabolic syndrome and incidence of type 2 diabetes (T2DM) in the Finnish Diabetes Prevention Study (DPS). Methods: DPS is a longitudinal study where 522 subjects with impaired glucose tolerance were randomized to either lifestyle intervention group or control group. DNA was available from 507 subjects (mean body mass index (BMI) 31.2±4.5 kg/m 2 , age 55 ± 7 years). The eight single-nucleotide polymorphisms (SNPs) were selected from HapMap database and genotyped by Taqman allelic discrimination protocol. The main results were confirmed in a larger cross-sectional study population (METSIM). In addition, the gene expression of IGFBP5 was studied in two previously published study populations (FUNGENUT and GENOBIN) of 124 subjects with insulin resistance (BMI 32.2 ± 3.5 kg/m 2 , age 57.7 ± 7.4 years). Results: Three out of eight IGFBP5 markers (rs9341234, rs3276 and rs11575134) were significantly associated with circulating adiponectin concentrations in men. Furthermore, mRNA expression studies of subcutaneous adipose tissue showed that mRNA concentrations of IGFBP5 correlated with adiponectin concentrations in all subjects and in women. None of the IGFBP5 SNPs were associated with T2DM. Conclusions: Our findings show that IGFBP5 has a gender-specific association with adiponectin, which may modulate the development of metabolic syndrome.

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“…The IGFBPs not only are carriers of the insulin-like growth factors but also are modulators of their bioavailability and of their autocrine and/or paracrine action (2,(4)(5)(6). Although the IGFBPs are ubiquitous, each is subject to its own developmental, tissue-specific, and hormonal regulation.…”

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confidence: 99%

“…They therefore play a role in the overall regulation of growth and differentiation during fetal and postnatal life (1,2). In biological fluids, they are noncovalently bound to high-affinity insulin-like growth factor binding proteins (IGFBPs), of which there are six distinct molecular species (3,4).…”

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confidence: 99%

Liver-specific expression of human insulin-like growth factor binding protein 1: functional role of transcription factor HNF1 in vivo.

Babajko

Tronche

Groyer

1993

Proc. Natl. Acad. Sci. U.S.A.

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Tissue-specific expression of insulin-like growth factor binding protein 1 (IGFBP-1) in the liver has been studied using differentiated (H41H and C2Rev7) and dedifferentiated (Hs and C2) rat hepatoma cell lines. Northern blot analysis showed that endogenous IGFBP-1 mRNA was expressed only in the differentiated cell lines. The first 341 base pairs 5' to the transcription initiation site of the human IGFBP-1 gene were inserted upstream of the chloramphenicol acetyltransferase reporter gene (pBP-1341). Expression of this gene from the human IGFBP-1 promoter was 10-16 times more efficient in the H411 line than in the other hepatoma cell lines and 40 and -12 times more so than in rat fibroblasts (FR3T3) and a human cervical carcinoma cell line (C33), respectively.Cotransfection of pBP-1341 and pRSV-HNF1 and/or pRSV-v-HNF1 (eukaryotic expression vectors that drive the synthesis of the liver-enriched trans-acting factor HNF1 or of v-HNF1, a related form) in C33 recipient cells yielded a 6-fold increase in IGFBP-1 promoter activity by HNF1 and a 2-fold increase by v-HNF1. These increases were dependent on the integrity of an HNF1 binding site located 58-74 nucleotides upstream of the cap site. Stimulation of promoter activity by cotransfection of both HNF1 and v-HNF1 fell between these values. Our results indicate that HNF1 is instrumental in human IGFBP-1 promoter activity in vivo and that v-HNF1 modulates this functional role.

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Insulinlike Growth Factor-Binding Proteins

Cited by 144 publications

References 166 publications

Inhibition of Insulin Receptor Activation by Insulin-like Growth Factor Binding Proteins

Inhibition of Insulin Receptor Activation by Insulin-like Growth Factor Binding Proteins

Association of sequence variations in the gene encoding insulin-like growth factor binding protein 5 with adiponectin

Liver-specific expression of human insulin-like growth factor binding protein 1: functional role of transcription factor HNF1 in vivo.

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