Cited by 536Growth Hormone and Insulin-like Growth FactorsFibroblast Growth Factor ResearchLiver physiology and pathology

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Insulin-like Growth Factor Binding Protein-1: Recent Findings and New Directions

Lee, P. D. K., Giudice, L. C., Conover, C. A., Powell, D. R.·1997·Experimental Biology and Medicine

DOI 10.3181/00379727-216-44182

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Abstract

In 1988, insulin-like growth factor-binding protein-1 (IGFBP-1) became the first characterized member of a group of structurally related soluble proteins which specifically bind and modulate the actions of the IGFs. Since then, a wealth of information has accumulated regarding the physiology of this dynamic serum protein. In this review, we update our 1993 summary (Lee PDK et al. Proc Soc Exp Biol Med 204:4-29) of the status of IGFBP-1 research. The IGFBP-1 protein sequence contains 12 N-terminal and 6 C-terminal cysteine residues which are conserved in other mammalian IGFBP-1 sequences and amongst other IGFBPs; both of the cysteine-rich regions are required for optimal IGF binding. The nonconserved IGFBP-1 midregion may act as both a hinge which defines ligand binding characteristics and as a specific target for protease activity. Integrin-binding and phosphorylation sites within the IGFBP-1 sequence have functional significance in vitro, but their physiologic relevance in vivo have not been defined. The human IGFBP-1 and IGFBP-3 genes are contiguous and located in close proximity to the homeobox A (HOXA) gene cluster on chromosome 7. The other IGFBP genes, located on chromosomes 2, 12, and 17, are also associated with HOX clusters, suggesting evolutionary linkage of the IGFBP and HOX gene families. Similarities between the hlGFBP-1 and phosphoenolpyruvate kinase (PEPCK) promoters, including regions conferring insulin, glucocorticoid, and cyclic adenosine-monophosphate responses, are consistent with our previous hypothesis that IGFBP-1 is involved in regulation of glucose metabolism. The tissue-specific patterns of IGFBP-1 gene expression in liver, kidney, decidua, and ovary may be due to stimulation of IGFBP-1 transcription by hepatic nuclear factor 1 (HNF1) proteins. Clinical and basic studies of IGFBP-1 physiology have been aided by several recently developed assay methods. Numerous investigations have confirmed that insulin, via inhibition of IGFBP-1 transcription, is the primary determinant of IGFBP-1 expression both in vitro and in viva IGF-I and IGF-II also have specific inhibitory effects on IGFBP-1 expression. Glucocorticoids and cAMP stimulate IGFBP-1 transcription, but these effects are observed only in conditions of low or absent insulin effect. Other stimulants of IGFBP-1 expression include thyroid hormones and epidermal growth factor. Phorbol ester stimulation of IGFBP-1 expression can supersede the effects of insulin in vitro; however, the mechanism and in vivo correlates of this effect have not been determined. Cytokines and, perhaps, growth hormones may affect IGFBP-1 expression, perhaps by altering the regulatory actions of insulin; this effect may have important clinical relevance. IGFBP-1 expression is upregulated in liver and (nonhuman) kidney during postinjury regeneration. The IGF-inhibitory actions of IGFBP-1 has been confirmed by numerous in vitro studies and several in vivo animal investigations, including administration of recombinant IGFBP-1 and IGFBP-1 transgenic models. IGFBP-1 has been shown to inhibit somatic linear growth, weight gain, tissue growth, and glucose metabolism. Moreover, IGFBP-1 appears to be a primary determinant of free IGF-I levels in serum. Excess levels of IGFBP-1 may contribute to growth failure in intrauterine growth restriction and in pediatric chronic renal failure, while low IGFBP-1 levels are associated with obesity and with cardiovascular risk factors in insulin resistance syndromes. Serum IGFBP-1 measurements may be useful biochemical marker in these pathologic conditions. IGFBP-1 is expressed in decidualized stromal cells of the uterine endometrium and in ovarian granulosa cells. IGFBP-1, together with IGFs, insulin, ovarian steroids, cytokines, and other factors, is involved in a complex system which regulates menstrual cycles, ovulation, decidualization, blastocyst implantation, and fetal growth. Models for the role of IGFBP-1 in female reproductive physiology are presented, and evidence for pathophysiologic roles in pre-eclampsia, polycystic ovarian syndrome, and uterine malignancy are reviewed. Very recent data indicates that IGFBP-1 undergoes regulated expression in human osteoblasts. Limited information also suggests that IGFBP-1 may be present in peripheral neurons, and that serum IGFBP-1 may increase during exercise and in critical ilIness. In summary, two major roles for IGFBP-1 in normal physiology can be constructed from current data: (i) As an “endocrine” factor, IGFBP-1 regulates the bio-availability of serum IGF-I, thereby modulating IGF-mediated tissue metabolism. The dominant regulation of IGFBP-1 expression by meal-related changes in hepatic insulin concentrations provides a dynamic link to substrate availability. (ii) As an autocrine/paracrine factor, IGFBP-1 appears to play a crucial role in the female reproductive system and, in particular, the sequence of events leading from ovulation to implantation to successful fetal outcom

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Background
Changes in gene expression in SIRT3 knockout liver cells
Tao, R., LECLERC, J., Yıldız, K., Park, S., Jung, B. H., Gius, D. R., & Özden, Ö. (2015) · TURKISH JOURNAL OF BIOLOGY · doi:10.3906/biy-1408-40 · Cited by 2
“The regulation of IGFBP-1 transcription is mainly controlled by insulin under basal conditions (Heemskerk et al., 1999) and its expression is upregulated in response to a number of inflammatory conditions (Lee et al., 1997; Scharf et al., 2004).”
Background
Molecular characterization and tissue expression profiles of insulin-like growth factor binding protein-1 (IGFBP-1) in Chinese alligator Alligator sinensis during the active and hibernating periods
Li, M., Meng, T., Peng, F., et al. (2018) · Biologia · doi:10.2478/s11756-018-0028-3 · Cited by 2
“All the 18 cysteines, involved in intradomain disulphide bond formation (Hwa et al. 1999), form a structural framework with surrounding residues to provide the functional specificity for IGF binding (Lee et al. 1997).”
Influential
Maternal-fetal conflict — lessons from a transgene
Giudice, L. C. (2002) · Journal of Clinical Investigation · doi:10.1172/jci200216389 · Cited by 2
Self-citation
Evaluation of binding capacity of circulating insulin-like growth factor binding protein-1b in salmonids using a ligand immunofunctional assay
Arimoto, M., Izutsu, A., Hara, A., & Shimizu, M. (2023) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/j.cbpa.2023.111488 · Cited by 2
The IGF-IGFBP system in aerobic exercise : with focus on skeletal muscle
Berg, U. (2007) · Figshare · Cited by 1
Clinical Uses of IGF-I and IGF Binding Protein Assays
Underwood, L. E. (1999) · Humana Press eBooks · doi:10.1007/978-1-59259-712-3_25 · Cited by 2
The GH/IGF-1 system during surgery and catabolism : Focus on metabolism and heart function
Wallin, M. K. E. B. (2007) · Figshare · Cited by 2
Epigenetics of Diabetic Nephropathy
Gu, H. F. (2017) · Springer eBooks · doi:10.1007/978-3-319-31143-2_27-1 · Cited by 1
Microarray analysis of differentially expressed genes in preeclamptic and normal placental tissues
Ma, K., Lian, Y., Zhou, S., et al. (2014) · Clinical and Experimental Obstetrics & Gynecology · doi:10.12891/ceog16432014 · Cited by 1
The Impact of Polycystic Ovarian Syndrome on Gestational Diabetes
Aust, S., & Ott, J. (2011) · InTech eBooks · doi:10.5772/23795 · Cited by 1
“Alterations in IGFBP-1 concentrations may be due to variations in insulin secretion or hepatic insulin sensitivity, both known to be important factors in glucose regulation (Lee et al., 1997).”
Background
Uterine disease in midlife and beyond: the menopausal transition and postmenopause
Polotsky, A. J., & Santoro, N. (2008) · CRC Press eBooks · doi:10.3109/9780203091500.054 · Cited by 2
Protein-restricted maternal diet during lactation decreases type I and type III tropocollagen synthesis in the skin of mice offspring
Yamane, T., Konno, R., Iwatsuki, K., et al. (2018) · Bioscience Biotechnology and Biochemistry · doi:10.1080/09168451.2018.1491288 · Cited by 1
“Because IGF-I bioavailability for target cells is modulated by IGFBPs which are present in tissues at levels sufficient to alter IGF-I action [9,10], not only tissue IGF-I but also IGFBP-1 levels are important factors that determine tissue response to IGF-I.”
Background
Epigenetics of Diabetic Nephropathy
Gu, H. F. (2019) · Springer eBooks · doi:10.1007/978-3-319-55530-0_27 · Cited by 1
Increase in Serum Total IGF-I and Maintenance of Free IGF-I Following Intentional Weight Loss in Pre-menopausal Women at Increased Risk of Breast Cancer
Harvie, M., Renehan, A. G., Frystyk, J., Flyvbjerg, A., Mercer, T., Malik, R., Adams, J. E., Cuzick, J. M., & Howell, A. (2010) · The Open Obesity Journal · doi:10.2174/1876823701002010063 · Cited by 1
Inflammation and the Insulin-like Growth Factor System at Very Preterm Birth. Implications for Early Morbidity and Development.
Pupp, I. H. (2008) · Lund University Publications (Lund University) · Cited by 1
Endogenous Hormone Metabolism and Endometrial Cancer
Kaaks, R., & Lukanova, A. (2005) · Nutrition and disease prevention · doi:10.1201/9781420026641.ch16 · Cited by 1
Does the Insulin‐Like Growth Factor System Interact with Prostaglandins and Proinflammatory Cytokines During Neurodegeneration?
Lackey, B. R., Gray, S. L., & Henricks, D. M. (2000) · Proceedings of The Society for Experimental Biology and Medicine · doi:10.1111/j.1525-1373.2000.22360.x · Cited by 1
Transposon insertion in pmel17 rewired skin and muscle transcriptomes in Mozambique tilapiaPreprint
Sun, F., Wang, L., & Yue, G. H. (2023) · Research Square · doi:10.21203/rs.3.rs-3204520/v1 · Cited by 1
Role of Growth Hormone Resistance and Impaired Insulin-like Growth Factor-I Bioavailability in the Pathogenesis of Cirrhosis and Its Complications
Donaghy, A. J. (2003) · Elsevier eBooks · doi:10.1016/b978-012525251-5/50023-3
Intra-ovarian Modification of FSH Action in the Human
Schipper, I. (1999) · RePub (Erasmus University Rotterdam)
Long-acting insulin analogs in type 1 diabetes : effects on metabolic control, endogenous insulin production and the GH-IGF-axis
Salemyr, J. (2015) · Figshare
Myocardial infarction and diabetes mellitus Studies on glucose lowering therapies and novel risk markers based on observations from the DIGAMI 2 trial
Mellbin, L. (2010) · Figshare
Genetic analyses of type 2 diabetes related metabolic risk factors : a twin study
Souren, N. Y. (2009) · Research Publications (Maastricht University) · doi:10.26481/dis.20090123ns
Western Blot und realtime PCR- basierte Identifizierung möglicher Hypertonie assoziierter Gene an einem definiertem Hypotoniemodell an Wistar-Kyoto Ratten
Furundzija, V. (2008) · Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver · doi:10.17169/refubium-12773
P-77 Relationships between serum insulin-like growth factor-I levels, blood pressure and glucose tolerance: an observational, exploratory study in 404 subjects
Colao, A., Somma, C. D., Cascella, T., Pivonello, R., Vitale, G., Grasso, L., Lombardi, G., & Savastano, S. (2008) · Growth Hormone & IGF Research · doi:10.1016/s1096-6374(08)70162-x
Low IGFBP-1 is a marker of impaired skin vascular response to both endothelial and non-endothelial stimulation in healthy males
Lehtihet, M., Jörneskog, G., Alvarsson, M., Båvenholm, P., Katz, A., Efendić, S., Östenson, C., Kuhl, J., & Brismar, K. (2009) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2009.04.009
The Sirtuins in Aging and Metabolic Regulation
LaGuire, T. C., & Reaves, S. K. (2013) · Food and Nutrition Sciences · doi:10.4236/fns.2013.46086
“IGF1 levels were significantly different between male WT and transgenic mice but not between female mice and these differences coincided with differences in expression levels of IGFBP1 [61], the molecule believed to be the main acute effector of IGF1 levels [62].”
Background
INFLUENCE OF ALCOHOL ON SOME APPETITE- REGULATING HORMONES IN MAN
Calissendorff, J. (2008)
Endogenous hormones in the etiology of ovarian and endometrial cancers
Lukanova, A. (2004) · DiVA at Umeå University (Umeå University)

Authors: Lee, P. D. K., Giudice, L. C., Conover, C. A., & Powell, D. R.
Affiliations: Mayo Clinic (US)
ORCID: Lee, P. D. K.
Giudice, L. C.
Conover, C. A.
Powell, D. R.
Venue: Experimental Biology and Medicine
Publisher: Frontiers Media SA
Published: 1997-12-01
Volume: 216
Issue: 3
Pages: 319-357
ISSN: 0071-3384 (ISSN-L)
1535-3702
1535-3699
DOI: 10.3181/00379727-216-44182
OpenAlex: W2036466897
Cited by: 523
References: 0
Citations by year: 2026: 1 · 2025: 4 · 2024: 8 · 2023: 4 · 2022: 6 · 2021: 10 · 2020: 8 · 2019: 11 · 2018: 10 · 2017: 19 · 2016: 16 · 2015: 16 · 2014: 11 · 2013: 17 · 2012: 14
FWCI: 16.84
Type: journal article
Language: en
Open access: closed
Locations: Experimental Biology and Medicine (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords: IGFBP-1, insulin-like growth factor, IGF binding, cysteine-rich region, protease cleavage, integrin binding, phosphorylation sites, IGFBP-3, chromosome 7, glucose metabolism, glucocorticoids, cyclic AMP, tissue-specific gene expression
MeSH terms: Amino Acid Sequence, Animals, Bone and Bones, Cartilage, Connective Tissue, Female, Gene Expression Regulation, Genitalia, Female, Genitalia, Male, Humans, Kidney, Liver, Male, Molecular Sequence Data, Organ Specificity, Substrate Specificity, Insulin-Like Growth Factor Binding Protein 1, Evolution, Molecular

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Insulin-like Growth Factor Binding Protein-1: Recent Findings and New Directions

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