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Gene Review

IGFBP1  -  insulin-like growth factor binding protein 1

Homo sapiens

Synonyms: AFBP, IBP-1, IBP1, IGF-BP25, IGF-binding protein 1, ...
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Disease relevance of IGFBP1


Psychiatry related information on IGFBP1

  • The possible effect of physical activity on IGFBP-1 requires further investigation [6].
  • The relationship between bone turnover and body weight, serum insulin-like growth factor (IGF) I, and serum IGF-binding protein levels in patients with anorexia nervosa [7].
  • IGFBP-1 is elevated in the blood as a result of sepsis, AIDS, excessive alcohol consumption, and diabetes and may, in part, be responsible for the wasting observed during these pathophysiological conditions [8].
  • It is well known that chronic alcohol abuse impairs liver function, but less is known about how an acute intake of moderate quantities of alcohol affects hepatic production of IGF-1 and IGFBP-1 [9].
  • This study examined the hypothesis that sustained physical activity and sleep deprivation superimposed on a short-term energy deficit would alter the IGFBP concentrations and alter the proportions of IGF-I circulating in ternary vs. binary molecular complexes [10].

High impact information on IGFBP1

  • IGFBP-1 interacts with alpha(5)beta(1) integrin, influencing cell adhesion and migration [11].
  • In the liverspecific igf-1 gene-deleted mouse model, postnatal growth and development are normal despite the marked reduction in circulating IGF-I and IGF-binding protein levels; free IGF-I levels are normal [12].
  • Use of mutagenesis to probe IGF-binding protein structure/function relationships [13].
  • Over the course of evolution, some members evolved into high-affinity IGF binders and others into low-affinity IGF binders, thereby conferring on the IGFBP superfamily the ability to influence cell growth by both IGF-dependent and IGF-independent means (Fig. 10) [14].
  • For example, the similarity of the IGFBP C terminus to the thyroglobulin type-I domain shows that the IGFBPs are also structurally related to numerous other proteins carrying the same domain (87) [14].

Chemical compound and disease context of IGFBP1


Biological context of IGFBP1

  • Genetic variation at the IGF2 and IGFBP1 loci could be among the factors responsible for the inter-individual differences observed in the response to long-term alterations in energy balance and should be further investigated in larger cohorts [20].
  • As a consequence of this event, the entire IGL locus, less the first three Vlambda elements, is translocated to chromosome 7, whereas the three remaining Vlambda elements on the der(22) are juxtaposed with IGFBP3 and IGFBP1 [21].
  • After correcting for gestational age, AF IGFBP1 remained strongly correlated with IGF-I and IGF-II (both p < 0.0001); their concentrations were many times higher in AF than in cord serum during the third trimester [2].
  • Using the chromatin immunoprecipitation technique, we demonstrated that liganded PGR was recruited to the IGFBP1 promoter region (-358 to -49) [22].
  • When FOXO1A expression was silenced using small interference RNA, IGFBP1 expression decreased in both HuF and HEC-1B cells [22].

Anatomical context of IGFBP1


Associations of IGFBP1 with chemical compounds

  • Insulin-like growth factor 2 (IGF2 ) and IGF-binding protein 1 (IGFBP1) gene variants are associated with overfeeding-induced metabolic changes [20].
  • In addition, pretreatment of ES cells with mepacrine decreased PRL/IGFBP1 expression and inhibited morphological change, whereas pretreatment with propranolol caused no changes, as compared to cAMP-treated cells, which suggests that PA induces decidualization through phospholipase A2 (PLA2G1B) [25].
  • On the other hand, the secretion of IGFBP1 was greatly stimulated by P and R [26].
  • Estrogen also increased IGFBP production, making it unlikely that the IGFBPs induced by estrogen in MCF-7 cells could function as major inhibitors of IGF action [5].
  • Moreover, from alignment of the predicted protein sequences of IGFBP-1 and IGFBP-2, extensive conservation of the distribution of cysteine residues is observed [27].
  • Individuals in the highest quartile at baseline for an algorithm incorporating fasting IGFBP-1, blood glucose, proinsulin and waist and height had a 40-fold increased risk of developing type 2 diabetes compared with the lowest quartile (95% CI 7.7-214) [28].

Physical interactions of IGFBP1

  • Western ligand blotting of column effluent samples revealed 37-/43-kDa IGFBP-3 primarily in the 150-kDa complex in serum and a marked reduction in the amount of the 37-/43-kDa IGFBP in PF [29].
  • In conclusion, mac25 specifically binds IGFs and constitutes a new member of the IGFBP family, IGFBP-7 [30].
  • We show here that tIGF-I, a non-IGFBP-binding analogue of IGF-1, is a more potent mitogenic stimulator of the keratinocyte cell line HaCaT than IGF-I, suggesting that keratinocytes produce IGFBPs that modulate their response to IGF-I [31].
  • All members of the IGFBP family bind IGF-I and IGF-II with about equal affinity [32].
  • IGFBP-2 is a form of binding protein that is structurally distinct from IGFBP-1 [33].

Enzymatic interactions of IGFBP1


Co-localisations of IGFBP1


Regulatory relationships of IGFBP1


Other interactions of IGFBP1


Analytical, diagnostic and therapeutic context of IGFBP1


  1. Erythrocytosis after renal transplantation represents an abnormality of insulin-like growth factor-I and its binding proteins. Brox, A.G., Mangel, J., Hanley, J.A., St Louis, G., Mongrain, S., Gagnon, R.F. Transplantation (1998) [Pubmed]
  2. IGF-I, IGF-II, IGF binding protein 1, and C-peptide in second trimester amniotic fluid are dependent on gestational age but do not predict weight at birth. Verhaeghe, J., Coopmans, W., van Herck, E., van Schoubroeck, D., Deprest, J.A., Witters, I. Pediatr. Res. (1999) [Pubmed]
  3. IGFBP1 and Follistatin-like 3 genes are significantly up-regulated in expression profiles of the IUGR placenta. Okamoto, A., Endo, H., Kalionis, B., Shinya, M., Saito, M., Nikaido, T., Tanaka, T. Placenta (2006) [Pubmed]
  4. Regulation of multiple insulin-like growth factor binding protein genes by 1alpha,25-dihydroxyvitamin D3. Matilainen, M., Malinen, M., Saavalainen, K., Carlberg, C. Nucleic Acids Res. (2005) [Pubmed]
  5. Regulation of insulin-like growth factor-binding protein (IGFBP) expression by breast cancer cells: use of IGFBP-1 as an inhibitor of insulin-like growth factor action. McGuire, W.L., Jackson, J.G., Figueroa, J.A., Shimasaki, S., Powell, D.R., Yee, D. J. Natl. Cancer Inst. (1992) [Pubmed]
  6. Lifestyle determinants of serum insulin-like growth-factor-I (IGF-I), C-peptide and hormone binding protein levels in British women. Allen, N.E., Appleby, P.N., Kaaks, R., Rinaldi, S., Davey, G.K., Key, T.J. Cancer Causes Control (2003) [Pubmed]
  7. The relationship between bone turnover and body weight, serum insulin-like growth factor (IGF) I, and serum IGF-binding protein levels in patients with anorexia nervosa. Hotta, M., Fukuda, I., Sato, K., Hizuka, N., Shibasaki, T., Takano, K. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  8. Stimulation of insulin-like growth factor binding protein-1 synthesis by interleukin-1beta: requirement of the mitogen-activated protein kinase pathway. Frost, R.A., Nystrom, G.J., Lang, C.H. Endocrinology (2000) [Pubmed]
  9. Insulin-like growth factor (IGF)-1 and IGF-binding protein-1 concentrations in serum of normal subjects after alcohol ingestion: evidence for decreased IGF-1 bioavailability. Röjdmark, S., Rydvald, Y., Aquilonius, A., Brismar, K. Clin. Endocrinol. (Oxf) (2000) [Pubmed]
  10. Differential responses of IGF-I molecular complexes to military operational field training. Nindl, B.C., Castellani, J.W., Young, A.J., Patton, J.F., Khosravi, M.J., Diamandi, A., Montain, S.J. J. Appl. Physiol. (2003) [Pubmed]
  11. Cellular actions of the insulin-like growth factor binding proteins. Firth, S.M., Baxter, R.C. Endocr. Rev. (2002) [Pubmed]
  12. The somatomedin hypothesis: 2001. Le Roith, D., Bondy, C., Yakar, S., Liu, J.L., Butler, A. Endocr. Rev. (2001) [Pubmed]
  13. Use of mutagenesis to probe IGF-binding protein structure/function relationships. Clemmons, D.R. Endocr. Rev. (2001) [Pubmed]
  14. The insulin-like growth factor-binding protein (IGFBP) superfamily. Hwa, V., Oh, Y., Rosenfeld, R.G. Endocr. Rev. (1999) [Pubmed]
  15. Hyperinsulinemia and decreased insulin-like growth factor-binding protein-1 are common features in prepubertal and pubertal girls with a history of premature pubarche. Ibáñez, L., Potau, N., Zampolli, M., Riqué, S., Saenger, P., Carrascosa, A. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  16. Total alanine-scanning mutagenesis of insulin-like growth factor I (IGF-I) identifies differential binding epitopes for IGFBP-1 and IGFBP-3. Dubaquié, Y., Lowman, H.B. Biochemistry (1999) [Pubmed]
  17. Insulin-like growth factor binding protein-1: recent findings and new directions. Lee, P.D., Giudice, L.C., Conover, C.A., Powell, D.R. Proc. Soc. Exp. Biol. Med. (1997) [Pubmed]
  18. Modulation by retinoic acid of insulin-like growth factor (IGF) and IGF binding protein expression in human SK-N-SH neuroblastoma cells. Babajko, S., Binoux, M. Eur. J. Endocrinol. (1996) [Pubmed]
  19. Concentrations of estrogens and IGFs in umbilical cord blood plasma: a comparison among Caucasian, Hispanic, and Asian-American females. Shibata, A., Harris, D.T., Billings, P.R. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  20. Insulin-like growth factor 2 (IGF2 ) and IGF-binding protein 1 (IGFBP1) gene variants are associated with overfeeding-induced metabolic changes. Ukkola, O., Sun, G., Bouchard, C. Diabetologia (2001) [Pubmed]
  21. Molecular cloning of a constitutional t(7;22) translocation associated with risk of hematological malignancy. Hill, A.S., MacCallum, P.K., Young, B.D., Lillington, D.M. Genes Chromosomes Cancer (2003) [Pubmed]
  22. Role of FOXO1A in the regulation of insulin-like growth factor-binding protein-1 in human endometrial cells: interaction with progesterone receptor. Kim, J.J., Buzzio, O.L., Li, S., Lu, Z. Biol. Reprod. (2005) [Pubmed]
  23. Characterization of the growth hormone receptor in human dermal fibroblasts and liver during development. Goodyer, C.G., Figueiredo, R.M., Krackovitch, S., De Souza Li, L., Manalo, J.A., Zogopoulos, G. Am. J. Physiol. Endocrinol. Metab. (2001) [Pubmed]
  24. Insulin-like growth factors and binding proteins in multiple sclerosis plaques. Gveric, D., Cuzner, M.L., Newcombe, J. Neuropathol. Appl. Neurobiol. (1999) [Pubmed]
  25. Phospholipase d1 as a key enzyme for decidualization in human endometrial stromal cells. Yoon, M.S., Koo, J.B., Jeong, Y.G., Kim, Y.S., Lee, J.H., Yun, H.J., Lee, K.S., Han, J.S. Biol. Reprod. (2007) [Pubmed]
  26. Production of insulin-like growth factor binding proteins (IGFBPs) by human endometrial stromal cell is stimulated by the presence of embryos. Liu, H.C., Mele, C., Catz, D., Noyes, N., Rosenwaks, Z. J. Assist. Reprod. Genet. (1995) [Pubmed]
  27. Cloning, sequence analysis and expression of a cDNA encoding a novel insulin-like growth factor binding protein (IGFBP-2). Binkert, C., Landwehr, J., Mary, J.L., Schwander, J., Heinrich, G. EMBO J. (1989) [Pubmed]
  28. Insulin-like growth factor-binding protein-1 in the prediction and development of type 2 diabetes in middle-aged Swedish men. Lewitt, M.S., Hilding, A., Ostenson, C.G., Efendic, S., Brismar, K., Hall, K. Diabetologia (2008) [Pubmed]
  29. The insulin-like growth factor system in human peritoneal fluid: its effects on endometrial stromal cells and its potential relevance to endometriosis. Giudice, L.C., Dsupin, B.A., Gargosky, S.E., Rosenfeld, R.G., Irwin, J.C. J. Clin. Endocrinol. Metab. (1994) [Pubmed]
  30. Synthesis and characterization of insulin-like growth factor-binding protein (IGFBP)-7. Recombinant human mac25 protein specifically binds IGF-I and -II. Oh, Y., Nagalla, S.R., Yamanaka, Y., Kim, H.S., Wilson, E., Rosenfeld, R.G. J. Biol. Chem. (1996) [Pubmed]
  31. A keratinocyte cell line synthesizes a predominant insulin-like growth factor-binding protein (IGFBP-3) that modulates insulin-like growth factor-I action. Wraight, C.J., Murashita, M.M., Russo, V.C., Werther, G.A. J. Invest. Dermatol. (1994) [Pubmed]
  32. Structural aspects of the IGFBP family. Drop, S.L., Schuller, A.G., Lindenbergh-Kortleve, D.J., Groffen, C., Brinkman, A., Zwarthoff, E.C. Growth Regul. (1992) [Pubmed]
  33. Three distinct forms of insulin-like growth factor binding proteins are released by decidual cells in culture. Clemmons, D.R., Thrailkill, K.M., Handwerger, S., Busby, W.H. Endocrinology (1990) [Pubmed]
  34. Insulin-like growth factor binding protein concentration and post-translational modification in embryological fluid. Miell, J.P., Jauniaux, E., Langford, K.S., Westwood, M., White, A., Jones, J.S. Mol. Hum. Reprod. (1997) [Pubmed]
  35. Peptide substrate specificities and protein cleavage sites of human endometase/matrilysin-2/matrix metalloproteinase-26. Park, H.I., Turk, B.E., Gerkema, F.E., Cantley, L.C., Sang, Q.X. J. Biol. Chem. (2002) [Pubmed]
  36. Pregnancy-associated plasma protein-A regulates myoblast proliferation and differentiation through an insulin-like growth factor-dependent mechanism. Kumar, A., Mohan, S., Newton, J., Rehage, M., Tran, K., Baylink, D.J., Qin, X. J. Biol. Chem. (2005) [Pubmed]
  37. Tissue transglutaminase facilitates the polymerization of insulin-like growth factor-binding protein-1 (IGFBP-1) and leads to loss of IGFBP-1's ability to inhibit insulin-like growth factor-I-stimulated protein synthesis. Sakai, K., Busby, W.H., Clarke, J.B., Clemmons, D.R. J. Biol. Chem. (2001) [Pubmed]
  38. Characterization of insulin-like growth factor binding protein-1 kinases from human hepatoma cells. Ankrapp, D.P., Jones, J.I., Clemmons, D.R. J. Cell. Biochem. (1996) [Pubmed]
  39. Most of the circulating insulin-like growth factors-I and -II are present in the 150 kDa complex during human pregnancy. Gargosky, S.E., Owens, P.C., Walton, P.E., Owens, J.A., Robinson, J.S., Wallace, J.C., Ballard, F.J. J. Endocrinol. (1991) [Pubmed]
  40. Effect of recombinant IGF binding protein-1 on primary cultures of human keratinocytes and fibroblasts: selective enhancement of IGF-1 but not IGF-2-induced cell proliferation. Kratz, G., Lake, M., Ljungström, K., Forsberg, G., Haegerstrand, A., Gidlund, M. Exp. Cell Res. (1992) [Pubmed]
  41. Production of an insulin-like growth factor (IGF)-inducible IGF-binding protein by human skin fibroblasts. Martin, J.L., Baxter, R.C. Endocrinology (1990) [Pubmed]
  42. Regulation of insulin-like growth factor binding protein-1 promoter activity by FKHR and HOXA10 in primate endometrial cells. Kim, J.J., Taylor, H.S., Akbas, G.E., Foucher, I., Trembleau, A., Jaffe, R.C., Fazleabas, A.T., Unterman, T.G. Biol. Reprod. (2003) [Pubmed]
  43. Insulin-like growth-factor-binding protein gene expression and protein production by human tumour cell lines. Reeve, J.G., Kirby, L.B., Brinkman, A., Hughes, S.A., Schwander, J., Bleehen, N.M. Int. J. Cancer (1992) [Pubmed]
  44. IGF-II and IGF binding protein (IGFBP-1, IGFBP-3) gene expression in fetal rhesus monkey tissues during the second and third trimesters. Lee, C.I., Goldstein, O., Han, V.K., Tarantal, A.F. Pediatr. Res. (2001) [Pubmed]
  45. Endogenous insulin-like growth factor (IGF) binding proteins cause IGF-1 resistance in cultured fibroblasts from a patient with short stature. Tollefsen, S.E., Heath-Monnig, E., Cascieri, M.A., Bayne, M.L., Daughaday, W.H. J. Clin. Invest. (1991) [Pubmed]
  46. Purification of a colon cancer cell growth inhibitor and its identification as an insulin-like growth factor binding protein. Culouscou, J.M., Shoyab, M. Cancer Res. (1991) [Pubmed]
  47. The N-terminal disulfide linkages of human insulin-like growth factor-binding protein-6 (hIGFBP-6) and hIGFBP-1 are different as determined by mass spectrometry. Neumann, G.M., Bach, L.A. J. Biol. Chem. (1999) [Pubmed]
  48. Insulin-like growth factor-1 and its binding proteins during a low-protein diet in chronic renal failure. Fouque, D., Le Bouc, Y., Laville, M., Combarnous, F., Joly, M.O., Raton, P., Zech, P. J. Am. Soc. Nephrol. (1995) [Pubmed]
  49. A potentially deleterious role of IGFBP-2 on bone density in aging men and women. Amin, S., Riggs, B.L., Atkinson, E.J., Oberg, A.L., Melton, L.J., Khosla, S. J. Bone Miner. Res. (2004) [Pubmed]
  50. Combined human growth hormone and lactulose for prevention and treatment of multiple organ dysfunction in patients with severe chronic hepatitis B. Ding, H.G., Shan, J., Zhang, B., Ma, H.B., Zhou, L., Jin, R., Tan, Y.F., He, L.X. World J. Gastroenterol. (2005) [Pubmed]
  51. Differential expression of insulin-like growth factor binding protein 1 and ferritin light polypeptide in gestational trophoblastic neoplasia: combined cDNA suppression subtractive hybridization and microarray study. Feng, H.C., Tsao, S.W., Ngan, H.Y., Xue, W.C., Chiu, P.M., Cheung, A.N. Cancer (2005) [Pubmed]
  52. Structure and chromosomal localization of human insulin-like growth factor-binding protein genes. Allander, S.V., Bajalica, S., Larsson, C., Luthman, H., Powell, D.R., Stern, I., Weber, G., Zazzi, H., Ehrenborg, E. Growth Regul. (1993) [Pubmed]
  53. Expression of insulinlike growth factor (IGF) and IGF-binding protein genes in human lung tumor cell lines. Reeve, J.G., Brinkman, A., Hughes, S., Mitchell, J., Schwander, J., Bleehen, N.M. J. Natl. Cancer Inst. (1992) [Pubmed]
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